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Los lípidos en deportistas representan la principal despensa energética y una fuente casi inagotable de energía durante el entrenamiento de resistencia, solo en deportes aeróbicos la demanda energética no produce subproductos que originen fatiga. Objetivos: Describir el perfil lipídico en niños y adolescentes deportistas de las selecciones de natación y tae kwon do del "Club de Regatas Lima". Material y Métodos: Se realizó un estudio descriptivo, prospectivo de corte transversal. Se evalúo a 77 deportistas, determinándose su perfil lipídico sérico: Colesterol total, HDL-C, LDL-C y triglicéridos en muestra de sangre venosa tomadas en ayuno nocturno de 12 horas y después de 72 horas de terminado el entrenamiento pre-competitivo; el dosaje se realizó enzimáticamente usando el método colorimétrico de punto final. Para interpretar los resultados se catalogó en tres niveles: Deseable, limítrofe y no deseable. Resultados: El colesterol total fue 172,57 ± 27,79 mg/dl en los 77 deportistas evaluados. El HDL-C medio fue 56,01 ± 1,01 mg/dl, LDL-C 94,61± 24,56mg/dl y triglicéridos 56,23±18,69 mg/dL. De los 77 deportistas, el 85,7% tuvieron HDL-C en nivel deseable 93,5%, triglicéridos en nivel deseable, y 49,4% colesterol total en niveles deseables No se encontró diferencias significativas en los valores de los grupos de natación y tae kwon do, con excepción del HDL-C en los juveniles.(Rev Med Hered 2007;18:22-27).

Background: Delirium severity scores are gaining acceptance for measuring delirium in the intensive care unit (ICU)., Objective: The aim of this study was to evaluate the concordance between the Confusion Assessment Method for the intensive care unit (CAM-ICU)-7 and the Intensive Care Delirium Screening Checklist (ICDSC) as delirium severity measurement tools., Methods: This was a prospective, comparative, observational multicentre study. This study was conducted in 18 Danish ICUs. Delirium was assessed in adult critically ill patients admitted to an ICU with a Richmond Agitation and Sedation Score (RASS) of -2 or above. ICU nurses assessed delirium with randomised paired delirium screening instruments, using the CAM-ICU, the ICDSC, and the CAM-ICU-7. The correlation between the CAM-ICU-7 and the ICDSC severity scores was evaluated for all predefined patient subgroups., Results: A total of 1126 paired screenings were conducted by 127 ICU nurses in 850 patients. The patients' median age was 70 years (interquartile range: 61-77), 40% (339/850) were female, and 54% (457/850) had at least one positive delirium score. Delirium severity ranges (CAM-ICU-7: 0-7; and ICDSC: 0-8) were positively correlated (Pearson's correlation coefficient, r = 0.83; p < 0.0001). The overall agreement between the CAM-ICU-7 and the ICDSC for delirium measurement (CAM-ICU-7: >2, and ICDSC: >3) was substantial (kappa = 0.74), but the agreement decreased to fair (kappa = 0.38) if a patient had a RASS less than 0., Conclusions: The agreement between the CAM-ICU-7 and the ICDSC for delirium severity measurement was substantial but might be affected by the patient's sedation and agitation level at the time of assessment., Implications for Practice: Both CAM-ICU-7 and ICDSC can be implemented for delirium severity measurement. Attention is warranted in both scores if a patient has a RASS of -2., Competing Interests: Conflict of interest The authors have no known competing interests for this manuscript. All authors have contributed substantially to the draughting of the protocol, data collection, data analyses, and interpretation of the results. All authors have critically revised this manuscript and approved this version for submission for publication. The Department of Intensive Care, Copenhagen University Hospital, Rigshospitalet, Denmark, has received funding from Novo Nordisk Fonden (0072048) for another research project. The Department of Anesthesiology and Intensive Care, Gødstrup Hospital received funding from Novo Nordisk Fonden (19OC0058277) for another research project., (Copyright © 2023 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: The aims of this bibliometric analysis were (1) a longitudinal analysis of the publication landscape in the field of pain (1975-2020) and (2) to characterize the overall publication profiles for two selected journals: European Journal of Pain and PAIN® utilizing an automated approach., Methods: Database searches in Scopus extracted all journals with 'pain' in their title. For the two specific journals, papers were manually/automatically profiled into preclinical, human and translational studies., Results: A gross list of 64 journals in the field of pain consisting of both active and ceased journals in Scopus were included in this analysis which identified 62,565 papers with approximately 4000 papers published/year. These papers include 2759 and 9156 papers in Eur. J. Pain and PAIN®, respectively. Currently, there are 24 active 'pain' journals. Authors/paper increase from 2 to 7 indicating a development from mono-disciplinary to multi-disciplinary studies. The overall publication profiles assessing preclinical, human (experimental/clinical) and translational papers in Eur. J. Pain and PAIN® were almost similar (14%, 75% and 10% versus 26%, 63% and 10%). Papers have changed over the years from mono-disciplinary studies (e.g. behavioural studies) to multi-disciplinary studies (e.g. combined behavioural and cell studies). After optimization, the search model matched the manual screening by 100%, 98% and 96% for the preclinical, clinical and healthy volunteer categories., Conclusions: Over the last 45 years, more than 60,000 pain-related papers have been published. Papers develop over the years from mono-disciplinary to multi-disciplinary studies. The overall publication profile including preclinical, human (experimental/clinical) and translational papers was almost similar in Eur. J. Pain and PAIN®., Significance: The bibliometric analysis of a pain journal provides information on which specific areas of research are published, how this may have changed over the years and how a journal is positioned compared with other journals in the field., (© 2023 European Pain Federation ‐ EFIC ®.)

Background: Delirium is common in critically ill patients with detrimental effects in terms of increased morbidity, mortality, costs, and human suffering. Delirium detection and management depends on systematic screening for delirium, which can be challenging to implement in clinical practice., Objectives: The aim of this study was to explore how nurses in the intensive care unit perceived the use of Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), the Confusion Assessment Method for the Intensive Care Unit-7 (CAM-ICU-7), and Intensive Care Delirium Screening Checklist (ICDSC) for delirium screening of patients in the intensive care unit., Methods: This was a cross-sectional, electronic-based survey of nurses' perceptions of delirium screening with the three different instruments for delirium screening. Nurses were asked to grade their perception of the usability of the three instruments and how well they were perceived to detect delirium and delirium symptom changes on a 1- to 6-point Likert scale. Open questions about perceived advantages and disadvantages of each instrument were analysed using the framework method., Results: One hundred twenty-seven of 167 invited nurses completed the survey and rated the CAM-ICU-7 as faster and easier than the ICDSC, which was more nuanced and reflected changes in the patient's delirium better. Despite being rated as the fastest, easiest, and most used, the CAM-ICU provided less information and was considered inferior to the CAM-ICU-7 and ICDSC. Using familiar instruments made delirium screening easier, but being able to grade and nuance the delirium assessment was experienced as important for clinical practice., Conclusions: Both the ICDSC and the CAM-ICU-7 were perceived well suited for detection of delirium and reflected changes in delirium intensity. The CAM-ICU was rated as fast and easy but inferior in its ability to grade and nuance the assessment of delirium. Emphasis on clinical meaningfulness and continued education in delirium screening are necessary for adherence to delirium management guidelines., Competing Interests: Conflict of interest Anne Højager Nielsen is funded by the Novo Nordisk Foundation, NNF 19OC0058277. Marie Oxenbøll Collet is funded by the Novo Nordisk Foundation, NNF21OC0072048. All other authors declare no conflict of interests., (Copyright © 2023 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Purpose: To determine whether the retinal nerve fiber layer thickness can be used as an indicator for systemic neurodegeneration in diabetes., Methods: We used existing data from 38 adults with type 1 diabetes and established polyneuropathy. Retinal nerve fiber layer thickness values of four scanned quadrants (superior, inferior, temporal, and nasal) and the central foveal thickness were extracted directly from optical coherence tomography. Nerve conduction velocities were recorded using standardized neurophysiologic testing of the tibial and peroneal motor nerves and the radial and median sensory nerves, 24-hour electrocardiographic recordings were used to retrieve time- and frequency-derived measures of heart rate variability, and a pain catastrophizing scale was used to assess cognitive distortion., Results: When adjusted for hemoglobin A1c, the regional thickness of the retinal nerve fiber layers was (1) positively associated with peripheral nerve conduction velocities of the sensory and motor nerves (all P < 0.036), (2) negatively associated with time and frequency domains of heart rate variability (all P < 0.033), and (3) negatively associated to catastrophic thinking (all P < 0.038)., Conclusions: Thickness of the retinal nerve fiber layer was a robust indicator for clinically meaningful measures of peripheral and autonomic neuropathy and even for cognitive comorbidity., Translational Relevance: The findings indicate that the thickness of the retinal nerve fiber layer should be studied in adolescents and people with prediabetes to determine whether it is useful to predict the presence and severity of systemic neurodegeneration.

We describe the commissioning of a new electron-ion coincidence spectrometer used to diagnose the photon beam from a plane grating monochromator beamline at the ASTRID2 synchrotron radiation facility. The spectrometer allows determination of the absolute photon intensity by calibration to the photoabsorption cross sections of known gases, such as the rare gases Ar, Kr, and Xe presented here. The spectrometer operates at very low pressure (∼10-8-10-9 mbar) and-due to the coincidence electron-ion detection scheme-the detector efficiencies can be determined routinely; hence, the spectrometer can be recalibrated swiftly. By variation of a single potential of the spectrometer, the content of higher order radiation in the monochromatized synchrotron radiation can be analyzed. The layout and operation of the synchrotron radiation beamline at ASTRID2 and its additional photon diagnostic units are additionally described., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Tobacco smoking-related diseases are estimated to kill more than 8 million people/year and most smokers are willing to stop smoking. The pharmacological approach to aid smoking cessation comprises nicotine replacement therapy (NRT) and inhibitors of the nicotinic acetylcholine receptor, which is activated by nicotine. Common side effects of oral NRT products include hiccoughs, gastrointestinal disturbances and, most notably, irritation, burning and pain in the mouth and throat, which are the most common reasons for premature discontinuation of NRT and termination of cessation efforts. Attempts to reduce the unwanted sensory side effects are warranted, and research discovering the most optimal masking procedures is urgently needed. This requires a firm mechanistic understanding of the neurobiology behind the activation of sensory nerves and their receptors by nicotine. The sensory nerves in the oral cavity and throat express the so-called transient receptor potential (TRP) channels, which are responsible for mediating the nicotine-evoked irritation, burning and pain sensations. Targeting the TRP channels is one way to modulate the unwanted sensory side effects. A variety of natural (Generally Recognized As Safe [GRAS]) compounds interact with the TRP channels, thus making them interesting candidates as safe additives to oral NRT products. The present narrative review will discuss (1) current evidence on how nicotine contributes to irritation, burning and pain in the oral cavity and throat, and (2) options to modulate these unwanted side-effects with the purpose of increasing adherence to NRT. Nicotine provokes irritation, burning and pain in the oral cavity and throat. Managing these side effects will ensure better compliance to oral NRT products and hence increase the success of smoking cessation. A specific class of sensory receptors (TRP channels) are involved in mediating nicotine's sensory side effects, making them to potential treatment targets. Many natural (Generally Recognized As Safe [GRAS]) compounds are potentially beneficial modulators of TRP channels., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Purpose: The superior and inferior tarsal muscles are sympathetically innervated smooth muscles. Long-term diabetes often leads to microvascular complications, such as, retinopathy and autonomic neuropathy. We hypothesized that diabetes induces (1) sympathetic paresis in the superior and inferior tarsal muscles and that this measure is associated with (2) the severity of diabetic retinopathy, (3) the duration of diabetes, and (4) autonomic function. In addition, association between the severity of retinopathy and autonomic function was investigated., Methods: Forty-eight participants with long-term type 1 diabetes and confirmed distal symmetrical polyneuropathy were included. Palpebral fissure heights were measured bilaterally in response to topically applied 10% phenylephrine to the right eye. The presence of proliferative diabetic retinopathy (PDR) or nonproliferative diabetic retinopathy and disease duration were denoted. Time and frequency derived heart rate variability parameters obtained from 24-hour continuous electrocardiography were recorded., Results: The difference in palpebral fissure heights between phenylephrine treated and untreated eyes (∆PFH) was 1.02 mm ± 0.29 (P = 0.001). The ∆PFH was significantly lower in the PDR group (0.41 mm ± 0.43 vs. 1.27 mm ± 1.0), F(1,35) = 5.26, P = 0.011. The ∆PFH was lower with increasing diabetes duration, r(37) = -0.612, P = 0.000. Further, the ∆PFH was lower with diminished autonomic function assessed as total frequency power in electrocardiogram (r = 0.417, P = 0.014), and sympathetic measures of very low (r = 0.437, P = 0.010) and low frequency power (r = 0.384, P = 0.025)., Conclusions: The ∆PFH is a simple ambulatory sympathetic measure, which was associated with the presence of PDR, disease duration, and autonomic function. Consequently, ∆PFH could potentially be an inexpensive and sensitive clinical indicator of autonomic dysfunction.

Although many proteins possess a distinct folded structure lying at a minimum in a funneled free energy landscape, thermal energy causes any protein to continuously access lowly populated excited states. The existence of excited states is an integral part of biological function. Although transitions into the excited states may lead to protein misfolding and aggregation, little structural information is currently available for them. Here, we show how NMR spectroscopy, coupled with pressure perturbation, brings these elusive species to light. As pressure acts to favor states with lower partial molar volume, NMR follows the ensuing change in the equilibrium spectroscopically, with residue-specific resolution. For T4 lysozyme L99A, relaxation dispersion NMR was used to follow the increase in population of a previously identified "invisible" folded state with pressure, as this is driven by the reduction in cavity volume by the flipping-in of a surface aromatic group. Furthermore, multiple partly disordered excited states were detected at equilibrium using pressure-dependent H/D exchange NMR spectroscopy. Here, unfolding reduced partial molar volume by the removal of empty internal cavities and packing imperfections through subglobal and global unfolding. A close correspondence was found for the distinct pressure sensitivities of various parts of the protein and the amount of internal cavity volume that was lost in each unfolding event. The free energies and populations of excited states allowed us to determine the energetic penalty of empty internal protein cavities to be 36 cal⋅Å -3 ., Competing Interests: The authors declare no competing interest.

The TRPA1 and TRPV1 receptors are important pharmaceutical targets for antipruritic and analgesic therapy. Obtaining further knowledge on their roles and interrelationship in humans is therefore crucial. Preclinical results are contradictory concerning coexpression and functional interdependency of TRPV1 and TRPA1, but no human evidence exists. This human experimental study investigated whether functional responses from the subpopulation of TRPA1 nociceptors could be evoked after defunctionalization of TRPV1 nociceptors by cutaneous application of high-concentration capsaicin. Two quadratic areas on each forearm were randomized to pretreatment with an 8% topical capsaicin patch or vehicle for 24 hours. Subsequently, areas were provoked by transdermal 1% topical capsaicin (TRPV1 agonist) or 10% topical allyl isothiocyanate ("AITC," a TRPA1 agonist), delivered by 12 mm Finn chambers. Evoked pain intensities were recorded during pretreatments and chemical provocations. Quantitative sensory tests were performed before and after provocations to assess changes of heat pain sensitivity. Imaging of vasomotor responses was used to assess neurogenic inflammation after the chemical provocations. In the capsaicin-pretreated areas, both the subsequent 1% capsaicin- and 10% AITC-provoked pain was inhibited by 92.9 ± 2.5% and 86.9 ± 5.0% (both: P < 0.001), respectively. The capsaicin-ablated skin areas showed significant heat hypoalgesia at baseline (P < 0.001) as well as heat antihyperalgesia, and inhibition of neurogenic inflammation evoked by both 1% capsaicin and 10% AITC provocations (both: P < 0.001). Ablation of cutaneous capsaicin-sensitive afferents caused consistent and equal inhibition of both TRPV1- and TRPA1-provoked responses assessed psychophysically and by imaging of vasomotor responses. This study suggests that TRPA1 nociceptive responses in human skin strongly depend on intact capsaicin-sensitive, TRPV1 fibers.

Carnivorous plants primarily use aspartic proteases during digestion of captured prey. In contrast, the major endopeptidases in the digestive fluid of the Venus flytrap (Dionaea muscipula) are cysteine proteases (dionain-1 to -4). Here, we present the crystal structure of mature dionain-1 in covalent complex with inhibitor E-64 at 1.5 Å resolution. The enzyme exhibits an overall protein fold reminiscent of other plant cysteine proteases. The inactive glycosylated pro-form undergoes autoprocessing and self-activation, optimally at the physiologically relevant pH value of 3.6, at which the protective effect of the pro-domain is lost. The mature enzyme was able to efficiently degrade a Drosophila fly protein extract at pH 4 showing high activity against the abundant Lys- and Arg-rich protein, myosin. The substrate specificity of dionain-1 was largely similar to that of papain with a preference for hydrophobic and aliphatic residues in subsite S2 and for positively charged residues in S1. A tentative structure of the pro-domain was obtained by homology modeling and suggested that a pro-peptide Lys residue intrudes into the S2 pocket, which is more spacious than in papain. This study provides the first analysis of a cysteine protease from the digestive fluid of a carnivorous plant and confirms the close relationship between carnivorous action and plant defense mechanisms., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

Background: Respiratory diseases exert a substantial burden on society, with newer drugs increasingly adding to the burden. Economic models are often used, but seldom reviewed., Purpose: To summarize economic models used in economic analyses of drugs treating moderate-to-severe/very severe asthma or chronic obstructive pulmonary disease (COPD)., Methods: This study searched Medline and Embase from inception to the end of February 2015 for cost-effectiveness/utility analyses that examined at least one drug against placebo, another drug, or other standard therapy in asthma or COPD. Two reviewers independently searched and extracted data with differences adjudicated via consensus discussion. Data extracted included model used and its qualities, validation methods, treatments compared, disease severity, analytic perspective, time horizon, data collection (pro- or retrospective), input rates and sources, costs and sources, planned sensitivity analyses, criteria for cost-effectiveness, reported outcomes, and sponsor., Results: This study analyzed 53 articles; 14 (25%) on asthma and 39 (75%) COPD. Markov models were commonly used for both asthma and COPD-related economic evaluations. Relatively few studies validated their model. For asthma-related studies, 10 examined inhaled corticosteroids and nine studied omalizumab. Placebo or standard therapy was the comparison in 11 studies and active drugs in the remainder., Conclusions: Few studies include validation of their models. Furthermore, controversy concerning some results was uncovered in this study, which needs to be avoided in the future.

•Increta in a prophylactic hysterectomy specimen for Lynch syndrome is rare.•Individualizing risk-reducing procedures after childbearing is important.•Shared decision making should include the timing of prophylactic surgery.•Minimizing surgical risks in the postpartum period should be discussed.

Musculoskeletal pain disorders are the second largest contributor to global disability underlining the significance of effective treatments. However, treating chronic musculoskeletal pain, and chronic joint pain (osteoarthritis (OA)) in particular, is challenging as the underlying peripheral and central pain mechanisms are not fully understood, and safe and efficient analgesic drugs are not available. The pain associated with joint pain is highly individual, and features from radiological imaging have not demonstrated robust associations with the pain manifestations. In recent years, a variety of human quantitative pain assessment tools (quantitative sensory testing (QST)) have been developed providing new opportunities for profiling patients and reaching a greater understanding of the mechanisms involved in chronic joint pain. As joint pain is a complex interaction between many different pain mechanisms, available tools are important for patent profiling and providing the basic knowledge for development of new drugs and for developing pain management regimes.

The archetypical venomous lizard species are the helodermatids, the gila monsters (Heloderma suspectum) and the beaded lizards (Heloderma horridum). In the present study, the gila monster venom proteome was characterized using 2D-gel electrophoresis and tandem mass spectrometry-based de novo peptide sequencing followed by protein identification based on sequence homology. A total of 39 different proteins were identified out of the 58 selected spots that represent the major constituents of venom. Of these proteins, 19 have not previously been identified in helodermatid venom. The data showed that helodermatid venom is complex and that this complexity is caused by genetic isoforms and post-translational modifications including proteolytic processing. In addition, the venom proteome analysis revealed that the major constituents of the gila monster venom are kallikrein-like serine proteinases (EC 3.4.21) and phospholipase A2 (type III) enzymes (EC 3.1.1.4). A neuroendocrine convertase 1 homolog that most likely converts the proforms of the previously identified bioactive exendins into the mature and active forms was identified suggesting that these peptide toxins are secreted as proforms that are activated by proteolytic cleavage following secretion as opposed to being activated intracellularly. The presented global protein identification-analysis provides the first overview of the helodermatid venom composition., Biological Significance: The helodermatid lizards are the classical venomous lizards, and the pharmacological potential of the venom from these species has been known for years; best illustrated by the identification of exendin-4, which is now used in the treatment of type 2 diabetes. Despite the potential, no global analyses of the protein components in the venom exist. A hindrance is the lack of a genome sequence because it prevents protein identification using a conventional approach where MS data are searched against predicted protein sequences based on the genome sequence. However, in the recent years the development of software tools for de novo sequencing and homology searches have improved significantly facilitating the first global analysis of the major protein components of helodermatid venom presented in this study. We have used a 2D-gel approach and determined the protein components in the 58 major spots resulting in the identification of 39 unique proteins. Of these, 19 have not previously been identified in helodermatid venom. The analysis provides results with impact on our understanding of the function and evolution of venom proteins, and serves as a basis for further unraveling of the pharmaceutical potential of the venom components., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Asthma and chronic obstructive pulmonary disease (COPD) are incurable diseases that impact quality-of-life., Objective: To summarize original research articles that measured or utilized preference-based utilities or disutilities according to disease severity., Methods: Medline and Embase were searched from inception until the end of November 2014. Two reviewers independently searched the literature with differences settled through discussion. Data extracted included utility scores as determined in original research categorized according to disease severity as well as disutilities associated with exacerbations or comorbidities. Data were tabulated and analyzed descriptively., Results: In total, 862 articles were identified, 790 were rejected, and 69 analyzed. There were 44 dealing with COPD and 25 with asthma. Average utilities determined by research were 0.828 ± 0.062, 0.765 ± 0.090, 0.711 ± 0.120, and 0.607 ± 0.120 for mild, moderate, severe, and very severe COPD, respectively. Utilities used in economic analyses were 0.866 ± 0.038, 0.770 ± 0.024, 0.739 ± 0.045, and 0.596 ± 0.075, respectively. Disutilities (annual) ranged from 0.002-0.378; major and minor exacerbations had respective disutilities of 0.287 and 0.108. For asthma patients, utilities were for 0.86 ± 0.32, 0.83 ± 0.065, and 0.74 ± 0.029, for mild, moderate, and severe disease, respectively., Conclusions: Utilities have been summarized according to severity category of asthma and COPD. These values should be useful for researchers undertaking economic analyses of these diseases.

Objectives: Clinical experience suggests that patients with osteoarthritis (OA) undergoing revision total knee arthroplasty (TKA) experience more chronic complications after surgery compared with patients receiving primary TKA. This study aimed to investigate the difference in pain, mobility, and quality of life (QoL) in patients after revision TKA compared with patients after primary TKA., Methods: A total of 99 OA patients after revision TKA surgery and 215 patients after primary TKA surgery were investigated in a cross-sectional study using: a pain description of current pain (non-existent, mild, moderate, severe, or unbearable), the pain intensity visual analogue scale, the Knee Society Score, and the Osteoarthritis Research Society International questionnaire., Results: Nineteen percent after primary TKA surgery and 47% after revision TKA surgery experienced severe to unbearable chronic postoperative pain. After revision TKA surgery patients reported higher pain intensities during rest (P=0.039), while walking (P=0.008), and on average over the last 24 hours (P=0.050) compared with the patients after primary TKA surgery. Patients after revision TKA surgery had reduced walking distance (P=0.001), increased use of walking aids (P=0.015), and showed an overall decreased QoL (P<0.001) compared with patients after primary TKA surgery. No significant improvement was found in walking distance (P=0.448) for patients before revision TKA surgery compared with after revision TKA surgery., Discussion: More than twice as many patients have pain after revision surgery compared with patients after primary TKA. Patients after revision TKA surgery have reduced function, poorer QoL, and higher pain intensity compared with patients after primary TKA surgery.

Human HtrA1 (high-temperature requirement protein A1) belongs to a conserved family of serine proteases involved in protein quality control and cell fate. The homotrimeric ubiquitously expressed protease has chymotrypsin-like specificity and primarily targets hydrophobic stretches in selected or misfolded substrate proteins. In addition, the enzyme is capable of exerting autolytic activity by removing the N-terminal insulin-like growth factor binding protein (IGFBP)/Kazal-like tandem motif without affecting the protease activity. In this study, we have addressed the mechanism governing the autolytic activity and find that it depends on the integrity of the disulfide bonds in the N-terminal IGFBP/Kazal-like domain. The specificity of the autolytic cleavage reveals a strong preference for cysteine in the P1 position of HtrA1, explaining the lack of autolysis prior to disulfide reduction. Significantly, the disulfides were reduced by thioredoxin, suggesting that autolysis of HtrA1 in vivo is linked to the endogenous redox balance and that the N-terminal domain acts as a redox-sensing switch.

When reaching toward a target, human subjects use slower movements to achieve higher accuracy, and this can be accompanied by increased limb impedance (stiffness, viscosity) that stabilizes movements against motor noise and external perturbation. In arthropods, the activity of common inhibitory motor neurons influences limb impedance, so we hypothesized that this might provide a mechanism for speed and accuracy control of aimed movements in insects. We recorded simultaneously from excitatory leg motor neurons and from an identified common inhibitory motor neuron (CI1) in locusts that performed natural aimed scratching movements. We related limb movement kinematics to recorded motor activity and demonstrate that imposed alterations in the activity of CI1 influenced these kinematics. We manipulated the activity of CI1 by injecting depolarizing or hyperpolarizing current or killing the cell using laser photoablation. Naturally higher levels of inhibitory activity accompanied faster movements. Experimentally biasing the firing rate downward, or stopping firing completely, led to slower movements mediated by changes at several joints of the limb. Despite this, we found no effect on overall movement accuracy. We conclude that inhibitory modulation of joint stiffness has effects across most of the working range of the insect limb, with a pronounced effect on the overall velocity of natural movements independent of their accuracy. Passive joint forces that are greatest at extreme joint angles may enhance accuracy and are not affected by motor inhibition., (Copyright © 2014 Calas-List et al.)

Translation of the analgesic efficacy of investigational neurotherapeutics from pre-clinical pain models into clinical trial phases is associated with a high risk of failure. Application of human pain biomarkers in early stages of clinical trials can potentially enhance the rate of successful translation, which would eventually reduce both length and costs of drug development after the pre-clinical stage. Human pain biomarkers are based on the standardized activation of pain pathways followed by the assessment of ongoing and paroxysmal pain, plus evoked responses which can be applied to healthy individuals and patients prior to and after pharmacological interventions. This review discusses the rationality and feasibility of advanced human pain biomarkers in early phases of drug development for pain management which is still an unmet medical need.

Predation plays a major role in energy and nutrient flow in the biological food chain. Plant carnivory has attracted much interest since Darwin's time, but many fundamental properties of the carnivorous lifestyle are largely unexplored. In particular, the chain of events leading from prey perception to its digestive utilization remains to be elucidated. One of the first steps after the capture of animal prey, i.e. the enzymatic breakup of the insects' chitin-based shell, is reflected by considerable chitinase activity in the secreted digestive fluid in the carnivorous plant Venus flytrap. This study addresses the molecular nature, function, and regulation of the underlying enzyme, VF chitinase-I. Using mass spectrometry based de novo sequencing, VF chitinase-I was identified in the secreted fluid. As anticipated for one of the most prominent proteins in the flytrap's "green stomach" during prey digestion, transcription of VF chitinase-I is restricted to glands and enhanced by secretion-inducing stimuli. In their natural habitat, Venus flytrap is exposed to high temperatures. We expressed and purified recombinant VF chitinase-I and show that the enzyme exhibits the hallmark properties expected from an enzyme active in the hot and acidic digestive fluid of Dionaea muscipula. Structural modeling revealed a relative compact globular form of VF chitinase-I, which might contribute to its overall stability and resistance to proteolysis. These peculiar characteristics could well serve industrial purposes, especially because of the ability to hydrolyze both soluble and crystalline chitin substrates including the commercially important cleavage of α-chitin., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: The human ultraviolet-B (UVB) experimental pain model induces cutaneous neurogenic inflammation, involves hyperalgesia, and is widely used as a pharmacological screening pain model., Aim: To estimate the test-retest reliability of the UVB pain model by application of a comprehensive set of vasomotor and quantitative sensory assessment methods and to estimate sample sizes required for parallel or crossover pharmacological screening studies when this model is considered to be applied., Methods: The upper arms of 15 healthy male volunteers were UVB irradiated with three times the minimal erythema dose. Neurogenic inflammation was assessed by measuring erythema index, superficial blood flow and skin temperature at baseline, 1 day, 2 days and 3 days post irradiation. Sensory changes were assessed by brush stroke, von Frey hairs, pressure algometry, heat-evoked pain, stimulus response function to weight calibrated pin-prick stimulation, and the area of secondary hyperalgesia. The experiment was repeated with a two-week interval. Systematic bias, Coefficient of variation (CV), and intra-class correlation (ICC) were calculated within and between UVB irradiations. The sample sizes for parallel and crossover studies were calculated., Results: Neurogenic inflammation (erythema index) and primary hyperalgesia (pin-prick stimulation) remained significant for 3 days, and were highly reproducible within and between the UVB irradiations resulting of low sample sizes (4-26) in both parallel and crossover studies., Conclusion: Based on sample size calculations, it is recommended to use the erythema index to assess neurogenic inflammation, and pin-prick stimulation for primary hyperalgesia for both parallel and crossover pharmacological screening studies.

Brief, localized, cutaneous, non-painful thermal stimuli can evoke a transient vasomotor response, causing increased cutaneous blood flow and elevated skin temperature. The aims of this study were to investigate 1) if cutaneous sensitization by topical application of capsaicin (TRPV1 receptor agonist) can facilitate the size, duration and spatial extent of this vasomotor response and 2) if males and females respond differently. Thermal pulses (43°C for 60 seconds) were applied on left/right volar forearms of 15 age-matched males and females. Skin temperature and cutaneous blood flow were measured 1, 5, 10, 15, and 30 minutes after heat application before and after topical capsaicin (1%, 30 min application) with contralateral arm serving as the control. Recordings were made from the region of interest at distances of 2, 4, 6, 8, and 10 cm from the capsaicin application site. Sensitization significantly enhanced skin temperature for up to 30 min and compared with non-sensitized skin at 10 min. Females showed the strongest response after sensitization, but the response lasted longer and spread more widely in males. The blood flow responses were significantly longer after capsaicin (from 5 to 30 minutes after thermal application). This increased blood flow extended outside the treated area up to 10 min after stimulation. After sensitization, the area under the blood flow response curves showed significantly stronger responses in females, spreading 4 cm outside the stimulation site. Cutaneous sensitizing caused prolonged and spatially expanded vasomotor responses to standardized thermal stimulation with sex specific differences.

Experiments can be complex and produce large volumes of heterogeneous data, which make their execution, analysis, independent replication and meta-analysis difficult. We propose a mathematical model for experimentation and analysis in physiology that addresses these problems. We show that experiments can be composed from time-dependent quantities, and be expressed as purely mathematical equations. Our structure for representing physiological observations can carry information of any type and therefore provides a precise ontology for a wide range of observations. Our framework is concise, allowing entire experiments to be defined unambiguously in a few equations. In order to demonstrate that our approach can be implemented, we show the equations that we have used to run and analyse two non-trivial experiments describing visually stimulated neuronal responses and dynamic clamp of vertebrate neurons. Our ideas could provide a theoretical basis for developing new standards of data acquisition, analysis and communication in neurophysiology.

Objectives: To examine whether disrupted regulation of REM sleep propensity is implicated in nightmare (NM) pathophysiology., Background: Heightened REM propensity induced by REM sleep deprivation is belied by increases in REM %, REM density and the dream-like quality of dream mentation during post-deprivation recovery sleep. Compromised regulation of REM sleep propensity may be a contributing factor in the pathophysiology of frequent NMs., Methods: A preliminary study of 14 subjects with frequent NMs (> or = 1 NM/week; 27.6+/-9.9 years) and 11 healthy control subjects (<1 NM/month; 24.3+/-5.3 years) was undertaken. Subjects completed home sleep/dream logs and underwent three nights of polysomnographic recording with REM sleep deprivation on night 2. Group differences were assessed for a battery of REM sleep and dream measures on nights 1 and 3., Results: Several measures, including #skipped early-night REM periods, REM latency, REM/NREM cycle length, early/late REM density, REM rebound, late-night REM% and dream vividness, suggested that REM sleep propensity was abnormally low for the frequent NM group throughout the 3-day study., Conclusions: Findings raise the possibility that REM anomalies recorded from NM sufferers sleeping in the laboratory environment reflect a disruption of one or more endogenous regulators of REM sleep propensity., (2009 Elsevier B.V. All rights reserved.)

Rapid eye movement (REM) sleep and dreaming may be implicated in cross-night adaptation to emotionally negative events. To evaluate the impact of REM sleep deprivation (REMD) and the presence of dream emotions on a possible emotional adaptation (EA) function, 35 healthy subjects randomly assigned to REMD (n = 17; mean age 26.4 +/- 4.3 years) and control (n = 18; mean age 23.7 +/- 4.4 years) groups underwent a partial REMD and control nights in the laboratory, respectively. In the evening preceding and morning following REMD, subjects rated neutral and negative pictures on scales of valence and arousal and EA scores were calculated. Subjects also rated dream emotions using the same scales and a 10-item emotions list. REMD was relatively successful in decreasing REM% on the experimental night, although a mean split procedure was applied to better differentiate subjects high and low in REM%. High and low groups differed - but in a direction contrary to expectations. Subjects high in REMD% showed greater adaptation to negative pictures on arousal ratings than did those low in REMD% (P < 0.05), even after statistically controlling sleep efficiency and awakening times. Subjects above the median on EA(valence) had less intense overall dream negativity (P < 0.005) and dream sadness (P < 0.004) than subjects below the median. A correlation between the emotional intensities of the morning dream and the morning picture ratings supports a possible emotional carry-over effect. REM sleep may enhance morning reactivity to negative emotional stimuli. Further, REM sleep and dreaming may be implicated in different dimensions of cross-night adaptation to negative emotions.

Native AMPA receptors (AMPARs) exhibit rapid and profound desensitization in the sustained presence of glutamate. Desensitization therefore contributes to short-term depression at synapses in which glutamate accumulates. At synapses that do not exhibit desensitization-dependent depression, AMPARs are thought to be protected against prolonged or repetitive exposure to synaptically released glutamate. At the cerebellar mossy fiber to granule cell (GC) synapse, in which high release probability and glutamate spillover produce a substantial buildup of glutamate concentration in the cleft ([Glut]cleft) during high-frequency transmission, only moderate desensitization of the phasic AMPAR EPSC occurs. To investigate how such currents are produced, we examined the kinetic properties of synaptic AMPARs in GCs using glutamate uncaging. Photolysis of 4-methoxy-7-nitroindolinyl-caged L-glutamate with large illumination spots produced step-like increases in [Glut]cleft that could be used to systematically probe AMPAR kinetics. At low levels of activation, synaptic AMPARs exhibited little desensitization. With larger activations, the desensitization time course became faster, but the level of desensitization was only weakly dependent on receptor occupancy. Indeed, a substantial desensitization-resistant current component remained (17%) in saturating glutamate. Photolysis with small illumination spots produced brief [Glut]cleft waveforms and transient AMPAR activations, similar to the EPSC current components. Paired-pulse uncaging with such spots revealed little desensitization after spillover-like activations and modest depression after activations that mimicked quantal and spillover components together. Our results show that GC AMPARs exhibit a resistance to desensitization at low occupancies and that this property is crucial for sustaining high-frequency transmission at a synapse in which glutamate accumulates.

Nightmares are common, occurring weekly in 4%-10% of the population, and are associated with female gender, younger age, increased stress, psychopathology, and dispositional traits. Nightmare pathogenesis remains unexplained, as do differences between nontraumatic and posttraumatic nightmares (for those with or without posttraumatic stress disorder) and relations with waking functioning. No models adequately explain nightmares nor have they been reconciled with recent developments in cognitive neuroscience, fear acquisition, and emotional memory. The authors review the recent literature and propose a conceptual framework for understanding a spectrum of dysphoric dreaming. Central to this is the notion that variations in nightmare prevalence, frequency, severity, and psychopathological comorbidity reflect the influence of both affect load, a consequence of daily variations in emotional pressure, and affect distress, a disposition to experience events with distressing, highly reactive emotions. In a cross-state, multilevel model of dream function and nightmare production, the authors integrate findings on emotional memory structures and the brain correlates of emotion., ((c) 2007 APA, all rights reserved)

Investigators since Freud have appreciated that memories of the people, places, activities and emotions of daily life are reflected in dreams but are typically so fragmented that their predictability is nil. The mechanisms that translate such memories into dream images remain largely unknown. New research targeting relationships between dreaming, memory and the hippocampus is producing a new theory to explain how, why and when we dream of waking life events.

The amplitude and shape of EPSC waveforms are thought to be important determinants of information processing and storage in the brain, yet relatively little is known about the origins of EPSC variability or how it affects synaptic signaling. We investigated the stochastic determinants of AMPA receptor-mediated EPSC variability at cerebellar mossy fiber-granule cell (MF-GC) connections by combining multiple-probability fluctuation analysis (MPFA) and deconvolution methods. The properties of MF connections with a single release site and the effects of the rapidly equilibrating competitive antagonist kynurenic acid on EPSCs suggest that receptors are not saturated by glutamate during a quantal event and that quanta sum linearly over a wide range of release probabilities. MPFA revealed an average of five vesicular release sites per MF-GC connection. Our results show that the time course of vesicular release is rapid (decay, tau = 75 micros) and independent of release probability, introducing little jitter in the shape or timing of the quantal component of the EPSC at physiological temperature. Moreover, the peak vesicular release rate per release site after an action potential (AP) (approximately 3 ms(-1)) is substantially higher than previously reported for central synapses. Interaction of amplitude fluctuations arising from quantal release and quantal size with the slower, low variability spillover-mediated current produce substantial variability in EPSC shape. Our simulations of MF-GC transmission suggest that quantal variability and transmitter spillover extend the voltage from which AP threshold can be crossed, improving reliability, and that fast vesicular release allows precise signaling across MF connections with heterogeneous weights.

The incorporation of memories into dreams is characterized by two types of temporal effects: the day-residue effect, involving immediate incorporations of events from the preceding day, and the dream-lag effect, involving incorporations delayed by about a week. This study was designed to replicate these two effects while controlling several prior methodological problems and to provide preliminary information about potential functions of delayed event incorporations. Introductory Psychology students were asked to recall dreams at home for 1 week. Subsequently, they were instructed to select a single dream and to retrieve past events related to it that arose from one of seven randomly determined days prior to the dream (days 1-7). They then rated both their confidence in recall of events and the extent of correspondence between events and dreams. Judges evaluated qualities of the reported events using scales derived from theories about the function of delayed incorporations. Average ratings of correspondences between dreams and events were high for predream days 1 and 2, low for days 3 and 4 and high again for days 5-7, but only for participants who rated their confidence in recall of events as high and only for females. Delayed incorporations were more likely than immediate incorporations to refer to events characterized by interpersonal interactions, spatial locations, resolved problems and positive emotions. The findings are consistent with the possibility that processes with circaseptan (about 7 days) morphology underlie dream incorporation and that these processes subserve the functions of socio-emotional adaptation and memory consolidation.

A review of the scientific literature clarifies several chronobiological features of dreaming. The literature supports the conclusions that dreaming 'intensity' and, to a lesser extent dream-like quality, is modulated by (1) a sinusoidal, 90-min ultradian oscillation, (2) a 'switch-like' circadian oscillation, (3) a 12-h circasemidian rhythm, and (4) a 28-day circatrigintan rhythm (for women). Further, access to dream memory sources appears to be modulated by (5) a 7-day circaseptan rhythm. Further study of these rhythmic influences on dreaming may help to explain diverse and often contradictory findings in the dream research literature, to clarify relationships between dreaming and waking cognitive processes, to explain relationships between disturbed phase relationships and dream disturbances and to shed new light on the problems of dreaming's functions and biological markers. Further chronobiological studies of dreaming will likely enable the development of theoretical models that explain how interactions between and within major levels of oscillation determine the variable characteristics of dreaming.

Fast- and slow-rising AMPA receptor-mediated EPSCs occur at central synapses. Fast-rising EPSCs are thought to be mediated by rapid local release of glutamate. However, two controversial mechanisms have been proposed to underlie slow-rising EPSCs: prolonged local release of transmitter via a fusion pore, and spillover of transmitter released rapidly from distant sites. We have investigated the mechanism underlying slow-rising EPSCs and the diffusion coefficient of glutamate in the synaptic cleft (Dglut) at cerebellar mossy fiber-granule cell synapses using a combination of diffusion modeling and patch-clamp recording. Simulations show that modulating Dglut has different effects on the peak amplitudes and time courses of EPSCs mediated by these two mechanisms. Slowing diffusion with the macromolecule dextran slowed slow-rising EPSCs and had little effect on their amplitude, indicating that glutamate spillover underlies these currents. Our results also suggest that under control conditions Dglut is approximately 3-fold lower than in free solution.

Relationships between Alpha (8-12 Hz) activity and cognitive processes during wakefulness raise the possibility of similar relationships between Alpha and cognitive activity during sleep. We hypothesized that Alpha power decreases during both Stage 2 and REM sleep would index the presence of sleep mentation in these stages. Absolute power for six classical EEG bands and three Alpha subbands was calculated for Stage 2 and REM sleep awakenings both with and without mentation recall. In both stages, recall was associated with lower Alpha power, especially with middle Alpha power (9.5-11.5 Hz). Unexpectedly, a similar effect for Delta power (0.5-4.0 Hz) was also observed. The Alpha effect may reflect cognitive elaboration active in the minutes preceding awakening; however, attention and memory processes cannot be excluded. The Delta effect is consistent with prior observations of regular linkages between Alpha and Delta power during sleep.

Background: Nightmares are common in posttraumatic stress disorder (PTSD), but they also frequently occur in idiopathic form. Findings associated with sleep disturbances in these two groups have been inconsistent, and sparse for idiopathic nightmares. The aim of the present study was to investigate whether sleep anomalies in PTSD sufferers with frequent nightmares (P-NM) differ from those observed in non-PTSD, idiopathic nightmare (I-NM) sufferers and healthy individuals., Methods: Sleep measures were obtained from nine P-NM sufferers, 11 I-NM sufferers, and 13 healthy control subjects. All participants slept in the laboratory for two consecutive nights where electroencephalogram, electro-oculogram, chin and leg electromyogram, electrocardiogram, and respiration were recorded continuously., Results: Posttraumatic nightmare sufferers had significantly more nocturnal awakenings than did I-NM sufferers and control subjects. Elevated indices of periodic leg movements (PLMs) during rapid eye movement (REM) and non-REM sleep characterized both P-NM and I-NM sufferers., Conclusions: Posttraumatic nightmare sufferers exhibit more nocturnal awakenings than do I-NM sufferers and control subjects, which supports the hypothesis of hyperarousal in sleep in PTSD sufferers; however, elevated PLM indices in both P-NM and I-NM sufferers suggest that PLMs may not be a marker of hyperarousal in sleep of PTSD sufferers. Rather, PLMs may be a correlate of processes contributing to intense negative dreaming.

It has been shown that realistic, localized painful sensations can be experienced in dreams either through direct incorporation or from past memories of pain. Nevertheless, the frequency of pain dreams in healthy subjects is low. This prospective study was designed to evaluate the occurrence and frequency of pain in the dreams of patients suffering from burn pain. Twenty-eight nonventilated burn victims were interviewed for 5 consecutive mornings during the first week of hospitalization. A structured-interview protocol was used to collect information on dream content, quality of sleep, and pain intensity and location. Patients were also administered the Impact of Event Scale to assess posttraumatic symptoms. Thirty-nine percent of patients reported 19 pain dreams on a total of 63 dreams (30%). Patients with pain dreams showed evidence of worse sleep, more nightmares, higher intake of anxiolytic medication, and higher scores on the Impact of Event Scale than did patents reporting dreams with no pain content. Moreover, patients with pain dreams also had a tendency to report more intense pain during therapeutic procedures. Although more than half of our sample did not report pain dreams, these results suggest that pain dreams do occur at a greater frequency in suffering populations than in normal volunteers. More importantly, dreaming about pain may be an added stress for burn patents and may contribute to both poor sleep and higher pain intensity, which could evolve into a cycle of pain-anxiety-sleeplessness.

Sleep disturbances are frequently reported in victims following burn injuries. This prospective study was designed to assess sleep quality and to examine its daily relationship to pain intensity within the first week of hospitalization. Twenty-eight non-ventilated patients were interviewed during 5 consecutive mornings (number of observations=140) to collect information about perceived quality of sleep (visual analogue scale, number of hours, number of awakenings, presence of nightmares). Pain intensity was assessed at rest (nighttime, morning, during the day) and following therapeutic procedures using a 0-10 numeric scale. Seventy-five percent of patients reported sleep disturbances at some point during the study although, in most patients, sleep quality was not consistently poor. Pooled cross-section regression analyses showed significant temporal relationships between quality of sleep and pain intensity such that a night of poor sleep was followed by a significantly more painful day. Pain during the day was not found to be a significant predictor of poor sleep on the following night. These results support previous findings that perceived quality of sleep following burn injury is poor. Moreover, they show a daily relationship between quality of sleep and acute burn pain in which poor sleep is linked to higher pain intensity during the day.

Numerous studies have replicated the finding of mentation in both rapid eye movement (REM) and nonrapid eye movement (NREM) sleep. However, two different theoretical models have been proposed to account for this finding: (1) a one-generator model, in which mentation is generated by a single set of processes regardless of physiological differences between REM and NREM sleep; and (2) a two-generator model, in which qualitatively different generators produce cognitive activity in the two states. First, research is reviewed demonstrating conclusively that mentation can occur in NREM sleep; global estimates show an average mentation recall rate of about 50% from NREM sleep--a value that has increased substantially over the years. Second, nine different types of research on REM and NREM cognitive activity are examined for evidence supporting or refuting the two models. The evidence largely, but not completely, favors the two-generator model. Finally, in a preliminary attempt to reconcile the two models, an alternative model is proposed that assumes the existence of covert REM sleep processes during NREM sleep. Such covert activity may be responsible for much of the dreamlike cognitive activity occurring in NREM sleep.

Study Objectives: This work assesses the prevalence and development of disturbing dreams among adolescents and the association of these dreams with anxiety., Design: Sex differences in prevalence were analyzed with chi-square analyses. Changes over time were assessed with Wilcoxon tests and cross-tabulation tables. Associations with anxiety and DSM-III-R symptoms were assessed with ANOVA designs., Setting: N/A., Participants: A total of 610 boys and girls rated their recall of disturbing and normal dreams at both 13 and 16 years of age. Subgroups of subjects were evaluated for anxiety symptoms at age 13 and for DSM-III-R symptoms of separation anxiety (SA), overanxious disorder (OD) and generalized anxiety disorder (GAD) at age 16., Interventions: N/A., Measurements and Results: The recall of disturbing dreams was more prevalent for girls than for boys at both ages, and increased over time for girls while it decreased for boys. The recall of normal dreams was also more prevalent for girls at both ages, but this difference could not fully account for the difference in recall of disturbing dreams. Normal dream recall increased from age 13 to 16 for both sexes. The frequent occurrence of disturbing dreams was associated with anxiety at age 13 and with GAD, SA and OD symptoms at age 16 for both sexes. Evidence of more numerous OD symptoms for girls with frequent disturbing dreams suggests that this form of anxiety may partially account for the observed sex difference in disturbing dream prevalence., Conclusions: The findings highlight a prevalence of disturbing dreams that is especially marked for adolescent girls. Unlike previous cross-sectional studies, which have found the same sex difference, this longitudinal design also calls attention to within-subjects changes in disturbing dream recall. The results also confirm that the frequent recall of disturbing dreams is associated with pathological symptoms of trait anxiety-apparently even as young as 13 years of age. Further study of disturbing dreams may contribute to understanding of associated pathophysiological factors which, too, vary by sex (e.g., PTSD, insomnia, depression).

We describe a 47-year-old man with annular plaques on the arms and torso that were treated as granuloma annulare, based on clinical and histopathologic findings. Exacerbation of the lesions during treatment with topical corticosteroids prompted a search for an infectious cause, which proved to be syphilis in the tertiary stage. The clinician should maintain a high index of suspicion for syphilis in the differential diagnosis of unusual annular skin lesions in a patient with noncaseating granulomas seen on skin biopsy.

EEG coherence was examined in relation to four measures of socioemotional dream content, including a new measure--the proportional representation of a character's face. Twenty-four healthy subjects, recorded for sleep stages and EEG activity, were awakened from REM sleep to report dream mentation and to rate it on these variables. Coherence scores were calculated for homologous interhemispheric electrode pairs (Fp1-Fp2, F3-F4, F7-F8, C3-C4, P3-P4, O1-O2, T3-T4, T5-T6) and for left and right intrahemispheric pairs for delta, theta, alpha, beta1, and beta2 frequencies. These were correlated with the mentation measures. Positive correlations were found between average interhemispheric coherence in most bands and the character face measure. A breakdown by gender revealed that this relationship was most evident for women, whereas for men positive correlations were observed between coherence and negative self-feeling. That similar relationships also obtained for both left and right intrahemispheric coherence is consistent with the hypothesis that dreamed socioemotional interactions reflect the integrative functioning of many brain regions in both hemispheres.

Neurofollicular hamartoma is a recently described lesion with a distinct pilosebaceous and spindle cell proliferation. Neurofollicular hamartoma is composed of spindle cells haphazardly arranged in a fibromyxoid stroma closely associated with an abnormal hyperplasia of folliculosebaceous units. Although this histologic pattern has been classified as "neurofollicular," all cases reported thus far have had only scattered spindle cells with S-100 positivity. We present a case of neurofollicular hamartoma with strong and diffusely positive staining of spindled cells for S-100 protein. This lesion also shows scattered positivity of spindle cells for monoclonal neuron specific enolase and synaptophysin. We interpret the results of immunostains of this lesion as evidence for neural differentiation. This case validates the concept of "neurofollicular" hamartoma.

Although numerous studies have investigated the content of laboratory and home dream reports, surprisingly little is known about the prevalence of various sensory modes in dreams. 49 men and 115 women completed a battery of questionnaires and kept a home dream diary for two to three consecutive weeks. Retrospective responses to the questionnaire indicate that approximately 33% of men and 40% of women recalled having experienced sensations of smell or taste in their dreams. A total of 3372 dream reports were collected and scored for unambiguous references to auditory, olfactory, and gustatory experiences. Auditory experiences were reported in approximately 53% of all dream reports. Olfactory and gustatory sensations occurred in approximately 1% of all dream reports. A significantly greater percentage of women than men reported one or more dreams containing references to olfactory sensations. The results lend support to previous studies which have shown that a variety of sensory experiences, although relatively rare, can occur in dreams.

The final traumatic event recalled by Anna O. during her treatment with Josef Breuer was a terrifying hallucination she once had of a black snake attacking her ailing father. This event has been variously interpreted as indicating an underlying psychodynamic conflict, as a temporal lobe seizure, and as an hypnotic confabulation. We argue, however, that the hallucination--during which Anna O.'s arm was reportedly "asleep" due to nerve blockage--was probably a sleep paralysis nightmare. Sleep paralysis nightmares continue to be overlooked or misdiagnosed in clinical practice, and, in recent years, have been implicated in the controversy surrounding memories of trauma and sexual abuse.

Troy and Ackerman defined the term sebaceoma (Am J Dermatopathol 1984: 6: 7-13) as benign neoplasm of basaloid cells with varying numbers of mature sebocytes. Steffen and Ackerman (Neoplasms with sebaceous differentiation. Philadelphia: Lee and Febiger, 1994: 401-425) illustrated many examples of sebaceoma, two of which had a reticulated and cribriform pattern. We report a case of sebaceoma from the scalp of a 52-year-old white female. Histologically, it displayed reticulated and cribriform basaloid epithelial islands. This is the third reported case of sebaceoma, to our knowledge, with these unusual features.

Cigarette smoking has been associated with sleep disturbances. However, little is known about how smoking affects restless legs syndrome (RLS) and sleep bruxism, two movement disorders associated with sleep. From a nationwide survey of 2,019 Canadian adults, we estimated the prevalence of smoking to be 36%. Although there was no difference between smokers and nonsmokers for RLS prevalence, almost twice as many smokers (12%) as nonsmokers (7%) were aware of experiencing sleep bruxism. The estimated risk of a smoker suffering from RLS was nonsignificant. On the other hand, the risk of a smoker grinding his or her teeth was moderate (odds ratio = 1.9). Analysis of sleep laboratory findings revealed no differences in motor RLS and periodic leg movements in sleep (PLMS) indices between smoking and nonsmoking patients; after adjustment for age, there were no differences in sleep efficiency, latency, number of awakenings, or the arousal index for the RLS/PLMS patients. Among those suffering from bruxism, smokers had more tooth-grinding episodes than did nonsmokers (35.0 vs. 7.0; p = 0.056); none of the sleep variables differentiated sleep bruxism smokers from nonsmokers. It appears that cigarette smoking does not influence RLS/PLMS, whereas the risk that smoking and tooth grinding are concomitant is moderate. Smoking was not significantly associated with more motor activity in RLS/PLMS, but more grinding was noted in sleep bruxism.

A recent case report of interhemispheric correlational measures in a callosotomized patient by Corsi-Cabrera, Trías, Guevara, Haro, and Hernández in 1995 provided evidence taken by the authors of the study to suggest that the corpus callosum may not be crucial to interhemispheric coupling. This conclusion was proposed even though (1) presurgical correlation measures necessary for evaluating coherence changes produced by surgery were not available for this subject and (2) previous studies presenting evidence inconsistent with their conclusions were not discussed. In view of these two shortcomings, the authors' conclusion concerning callosal function may be premature.

Previously we pointed out similarities between patterns of delayed incorporations of daytime stimuli into dreams and delayed memory processes in rats. In commenting upon this article, Roll argued that this reductionistic leap is unwarranted. We contend that it would be remiss not to make note of this potential connection, especially in view of recent major contributions of animal research to the understanding of REM sleep and dreams. We also suggest that the disruption-avoidance-adaptation model constitutes a preferable psychological explanation for the dream-lag effect than Roll's psychoanalytic model of repression and repetition compulsion.