Dissociating the contributions of slow-wave sleep and rapid eye movement sleep to emotional item and source memory.

Sleep benefits the consolidation of emotional memories, and this influence is commonly attributed to the rapid eye movement (REM) stage of sleep. However, the contributions of sleep stages to memory for an emotional episode may differ for the event per se (i.e., item memory), and the context in which it occurred (source memory). Here, we examined the effects of slow wave sleep (SWS) and REM sleep on the consolidation of emotionally negative and neutral item (picture recognition) and source memory (recall of picture-location and picture-frame color association) in humans. In Study 1, the participants (n=18) learned 48 negative and 48 neutral pictures which were presented at specific locations and preceded by colored frames that had to be associated with the picture. In a within-subject design, learning was either followed by a 3-h early-night SWS-rich or by a late-night REM sleep-rich retention interval, then retrieval was tested. Only after REM-rich sleep, and not after SWS-rich sleep, was there a significant emotional enhancement, i.e., a significantly superior retention of emotional over neutral pictures. On the other hand, after SWS-rich sleep the retention of picture-frame color associations was better than after REM-rich sleep. However, this benefit was observed only for neutral pictures; and it was completely absent for the emotional pictures. To examine whether this absent benefit reflected a suppressive effect of emotionality on associations of minor task relevance, in Study 2 we manipulated the relevance of the picture-frame color association by combining it with information about monetary reward, following otherwise comparable procedures. Here, rewarded picture-frame color associations were equally well retained over SWS-rich early sleep no matter if the frames were associated with emotional or neutral pictures. Results are consistent with the view that REM sleep favors the emotional enhancement of item memory whereas SWS appears to contribute primarily to the consolidation of context-color information associated with the item.

[Development of a claim form for the initiation of post-treatment rehabilitation for nationwide use by all reimbursement agencies: a report and plea for reducing administrative barriers]. / Entwicklung eines bundeseinheitlichen und kostenträger- übergreifenden Antragsformulars für die Einleitung der Anschlussrehabilitation: Projektbericht und Plädoyer zum Abbau administrativer Hürden.

We describe the results of a survey of claim forms that are used when starting rehabilitation following inpatient treatment and of an evaluation of a claim form developed on the basis of the results. The survey of different existing forms shows a high overlapping in content, suggesting the possibility of unification to one claim form that can be accepted by all insurers. In analogy to the Delphi method criteria for evaluation were consented and applied by the author group to assess the relevance of the claim forms content items for the process of initiating rehabilitation. A group of further experts added their evaluations. We prioritised the results and extracted the essential contents to conceive a unified claim form eligible for all types of rehabilitation. The claim form was discussed in 3 focus groups, revised accordingly and tested in the Hannover Medical School. Test results show that all relevant information is asked for and that the form is well manageable. The users' request for an IT-based solution and further ideas for improvement were integrated into the revised and validated version of the claim form. It is now available for all stake holders, in particular for insurers, as a means to improve quality of care and efficiency by standardisation of rehabilitation claim forms.

[World War II and current care provision: impact of war-related trauma on present professional care situations]. / Zweiter Weltkrieg und pflegerische Versorgung heute : Einfluss von Kriegstraumatisierungen auf professionelle Pflegesituationen.

BACKGROUND: This study represents the first empirical research into the impact of war-related trauma on present professional care situations in Germany. METHODS: A total of 105 professional caregivers from North Rhine-Westphalia were questioned in a standardized form about the impact of war-related trauma on the daily work. RESULTS: Of the professional caregivers questioned 82%reported that they were already caring for a person suffering from post-war trauma and 77% stated that war-related trauma had an impact on the daily work. Altogether 63% reported that war-related trauma is highly significant for the daily work. The professional caregivers reported that there was often a lack of knowledge and awareness of the topic among colleagues. CONCLUSIONS: The study showed that there is a need for increasing awareness and providing further staff education and training regarding the treatment of people suffering from (war-related) trauma in order to ensure adequate care for those concerned.

The role of REM sleep in the processing of emotional memories: evidence from behavior and event-related potentials.

Emotional memories are vividly remembered for the long-term. Rapid eye movement (REM) sleep has been repeatedly proposed to support the superior retention of emotional memories. However, its exact contribution and, specifically, whether its effect is mainly on the consolidation of the contents or the processing of the affective component of emotional memories is not clear. Here, we investigated the effects of sleep rich in slow wave sleep (SWS) or REM sleep on the consolidation of emotional pictures and the accompanying changes in affective tone, using event-related potentials (ERPs) together with subjective ratings of valence and arousal. Sixteen healthy, young men learned 50 negative and 50 neutral pictures before 3-h retention sleep intervals that were filled with either SWS-rich early or REM sleep-rich late nocturnal sleep. In accordance with our hypothesis, recognition was better for emotional pictures than neutral pictures after REM compared to SWS-rich sleep. This emotional enhancement after REM-rich sleep expressed itself in an increased late positive potential of the ERP over the frontal cortex 300-500 ms after stimulus onset for correctly classified old emotional pictures compared with new emotional and neutral pictures. Valence and arousal ratings of emotional pictures were not differentially affected by REM or SWS-rich sleep after learning. Our results corroborate that REM sleep contributes to the consolidation of emotional contents in memory, but suggest that the affective tone is preserved rather than reduced by the processing of emotional memories during REM sleep.

Pain Levels of Women Diagnosed with Endometriosis: Is There a Difference in Younger Women?

STUDY OBJECTIVE: Early diagnosis and treatment of endometriosis affecting adolescent women are important in preventing chronic pain. Our aim was to analyze the clinical characteristics and severity of symptoms in adolescent patients with endometriosis compared with older patients. METHODS: This single-center retrospective cohort study in a tertiary referral hospital analyzed women whose first consultation at the certified endometriosis center of Bern University Hospital between January 2017 and December 2020 resulted in the clinical diagnosis of endometriosis. Patients, divided into 2 groups by age, reported visual analog scale (VAS) scores for noncyclic pelvic pain, dysmenorrhea, dyschezia, dysuria, and dyspareunia. The symptom types and severity in the 2 groups were compared. The young patients with endometriosis were analyzed in greater detail, comparing VAS scores and types of endometriosis. RESULTS: From a total of 826 patients, 144 (17.4%) patients 24 years old or younger and 682 (82.6%) patients over 24 years old were compared. The younger patients reported significantly higher pain scores for dysmenorrhea (VAS 7.3 vs 6.6; P = .015), dyspareunia (VAS 4.6 vs 3.4; P = .001), and noncyclic pelvic pain (VAS 4.3 vs 3.7; P = .032) compared with the older patient collective. Similar results were found when excluding patients with hormonal treatment. CONCLUSION: Young patients with clinically diagnosed endometriosis have significantly higher dysmenorrhea and dyspareunia pain levels than older patients. By acknowledging and understanding this, early diagnosis and adequate treatment can be promoted. Dyspareunia in adolescents in particular merits clinical attention.

New aspects of the molecular constituents of tissue barriers.

Epithelial and endothelial tissue barriers are based on tight intercellular contacts (Tight Junctions, TJs) between neighbouring cells. TJs are multimeric complexes, located at the most apical border of the lateral membrane. So far, a plethora of proteins locating at tight intercellular contacts have been discovered, the role of which has just partly been unraveled. Yet, there is convincing evidence that many TJ proteins exert a dual role: They act as structural components at the junctional site and they are involved in signalling pathways leading to alterations of gene expression and cell behaviour (migration, proliferation). This review will shortly summarize the classical functions of TJs and TJ-related proteins and will introduce a new category, termed the "non-classical" functions of junctional proteins. A particular focus will be directed towards the nuclear targeting of junctional proteins and the downstream effects elicited by their intranuclear activities.

Calcein assay: a high-throughput method to assess P-gp inhibition.

Transporter mediated drug-drug interactions (tDDI) mediated by ABCB1 have been shown to be clinically relevant. Hence, the assessment of the ABCB1 tDDI potential early in the drug development process has gained interest. We have evaluated the Calcein assay as a means of assessing the ABCB1 tDDI that is amenable to high throughout and compared it with the monolayer efflux assay. We found the Calcein assay, when performed in K562MDR cells using the protocol originally published more sensitive than digoxin transport inhibition in MDCKII-MDR1 cells. Application of the Calcein assay to cell lines containing different amounts of ABCB1, yielded IC(50) values that varied 10-100-fold. The differences observed for IC(50) values for the same compounds were in the following rank order: IC(50, MDCKII-MDR1) >IC(50, K562MDR)>IC(50, hCMEC/D3). Higher IC(50) values were obtained in cells with higher ABCB1 expression. The Calcein assay is a high-throughput alternative to digoxin transport inhibition as it appears to have a comparable selectivity but higher sensitivity than previously published digoxin transport inhibition in MDCKII-MDR1 cells. In addition, it can be performed in a barrier-specific manner highlighting the dependence of ABCB1 IC(50) values on different ABCB1 expression levels.

Targeting of the kynurenic acid across the blood-brain barrier by core-shell nanoparticles.

Core-shell nanoparticles (CSNPs) were developed to get over therapeutic amount of kynurenic acid (KYNA) across the blood-brain barrier (BBB). Bovine serum albumin (BSA) was used as core for encapsulation of KYNA and the BSA/KYNA composite was finally encapsulated by poly(allylamine) hydrochloride (PAH) polymer as shell. In the interest of the optimization of the synthesis the BSA and KYNA interaction was studied by two-dimensional surface plasmon resonance (SPR) technique as well. The average size of d~100 nm was proven by dynamic light scattering (DLS) and transmission electron microscopy (TEM), while the structure of the composites was characterized by fluorescence (FL) and circular dichroism (CD) spectroscopy. The in vitro release properties of KYNA were investigated by a vertical diffusion cell at 25.0 °C and 37.5 °C and the kinetic of the release were discussed. The penetration capacity of the NPs into the central nervous system (CNS) was tested by an in vitro BBB model. The results demonstrated that the encapsulated KYNA had significantly higher permeability compared to free KYNA molecules. In the neurobiological serial of in vivo experiments the effects of peripherally administered KYNA with CSNPs were studied in comparison with untreated KYNA. These results clearly proved that KYNA in the CSNPs, administrated peripherally is suitable to cross the BBB and to induce electrophysiological effects within the CNS. As the neuroprotective properties of KYNA nowadays are proven, the importance of the results is obvious.

Regulation of proteolytic activity induced by inflammatory stimuli in lung epithelial cells.

A large number of chronic lung diseases such as asthma bronchiale are associated with alveolar and/or bronchial inflammation accompanied by a damage of the alveolocapillary barrier. In this process proteolytic mechanisms may play a crucial role. The aim of the present study was to assess the role of TNF-alpha on the proteolytic activity of pulmonary epithelial cells and to find possible intracellular signaling pathways which may mediate the effect of TNF-alpha. For our studies we have used the A549 human lung epithelial cell line. Plasminogen activator and metalloproteinase activity was measured using zymography. TNF-alpha induced a time and concentration dependent activation of the urokinase type plasminogen activator (u-PA) and tissue type plasminogen activator (t-PA) activity in A549 cells. This effect could be blocked completely by dexamethasone and was reduced significantly by the Rho-kinase inhibitor Y27632. Similarly, an increased activity in the culture medium of the 72 kDa MMP-2 in response to TNF-alpha could be observed as well. This could be reduced by dexamethasone and Y27632. Our results show that TNF-alpha is at least partly responsible for an increased proteolytic activity and beside corticosteroids Rho-kinase may constitute a potential target for future therapeutical approaches.

Development from birth to 3 years of age of 15 children at high risk for central nervous system dysfunction. Interim report.

The purposes of this study were to determine if a group of infants at high risk for later developmental abnormality could be selected on the basis of large numbers of serious neonatal problems, ascertain how early developmental outcome could be predicted, and document the development of the infants longitudinally during the first year of life. Fifteen infants were selected on the basis of high scores on a neonatal risk assessment scale. They were examined with a variety of developmental tests at regular intervals during their first year, at age 2 years, and at age 3 years. The results suggest that the selection process successfully identified a group of infants with developmental problems and that motor performance at 3 months was predictive of neurologic outcome at 3 years. Different patterns of neuromotor development in the first year were identified among those infants with severe cerebral palsy, those with milder neurologic problems, and those with apparently normal outcome.

Electromyographic and cinematographic analysis of movement from a kneeling to a standing position in healthy 5- to 7-year-old children.

Physical therapists often use transitional postures such as half-kneeling to help children with movement dysfunction attain an upright posture. Little is known, however, about how healthy children activate lower extremity muscles to move the hip, knee, and ankle joints as they move from kneeling through half-kneeling to stand up against gravity. The purpose of this study was to describe movement from kneeling to standing in 10 healthy 5- to 7-year-old children. Electromyography was used to record the activity of four lower extremity muscles. Cinematography was used to record joint motion of the hip, knee, and ankle of the leg initiating movement, in addition to trajectories of specific anatomical landmarks as the children rose from a kneeling to a standing position. Greater active range of motion of the hip, knee, and ankle was necessary to move from a kneeling to a standing position using the half-kneel transitional posture than is required during normal gait. The activation patterns of the gastrocnemius, tibialis anterior, rectus femoris, and biceps femoris muscles of the leg initiating movement exhibited variability among subjects during the kneel-to-stand movement. Maximum joint range of motion and position of the hip, knee, and ankle joints at specific points in the movement exhibited less variability than patterns of muscle activation. The results showed that movement from a kneeling to a standing position in healthy children is quantifiable and can be used to help determine what normal components of movement are necessary to successfully master this movement against gravity that is antecedent to ambulation. Further studies are needed to investigate antigravity movement in younger children and in children with movement dysfunction to more fully understand normal and abnormal movement in children.

Preparation of physical therapists to work with handicapped infants and their families: current status and training needs.

The purposes of this study were to determine the current status of physical therapists' preparation to work with handicapped and at-risk infants and their families and to identify needs for infant- and family-focused training materials and curricula. Results of a telephone survey of 73 physical therapy programs and a follow-up mail survey of 14 physical therapy programs with infancy specialization options are presented. Students in entry-level programs and postprofessional master's degree programs with infancy specializations commonly received instruction in infancy-related topics. Many students received minimal or no exposure to family-related content. Family assessment and intervention were identified as the areas of highest priority for development of training materials and curricula. The results of this study provide direction for the design of infant- and family-focused training materials and curricula in physical therapy.

Stability of Bayley Motor Scale scores in the first year of life.

The purpose of this study was to determine whether Bayley Motor Scale scores were stable in infants during the first year of life, that is, whether each individual infant's score was essentially the same at each of the five test ages. Subjects were 15 low-risk and 8 high-risk infants with Bayley Scales of Infant Development Motor Scale scores at 2, 3, 4, 8, and 12 months. All high-risk and most low-risk infants also had outcome scores at either 24 or 36 months. For the group as a whole, and for all infants with "normal" outcomes, subjects did not change ranks over the six test ages (ie, high-scoring infants' ranks remained high and low-scoring infants' ranks remained low), but scores varied significantly from test to test. Scores of infants with "non-normal" outcomes did not vary significantly from test to test. The highest and lowest scores of 75% of the infants with normal outcomes and 57% of the infants with non-normal outcomes differed significantly. Four patterns of variations of Bayley Motor Scale scores over the five test ages of the first year after birth were identified. The first pattern included three infants with the most stable scores. The three remaining patterns were different from each other, but a consistent feature of each was a peak at 4 months. Finally, scores at 3 and 8 months were best able to correctly identify outcome. A single Bayley Motor Scale score may not reflect an infant's true abilities; some factor may be inflating scores at age 4 months.

[Hyperinsulinism and lipid changes in the early stages of essential arterial hypertension]. / Hiperinsulinemia y alteraciones lipídicas en etapas tempranas de la hipertensión arterial esencial.

The purpose of this study was to evaluate the presence of insulin-resistance in non-obese, non-diabetic patients with mild to moderate essential arterial hypertension of recent diagnosis and without prior pharmacological treatment and its relationship with the lipid alteration found in those patients. Twenty-one controls (9 M/12F) and twenty-nine patients (19 M/10 F) were studied. The control group presented mean age: 29 +/- 1.5 years, BMI: 23.9 +/- 0.46 Kg/m2, SBP: 112.6 +/- 2.9 mm Hg, DBP: 68.0 +/- 2.9 mm Hg. The patient group presented mean age: 35 +/- 1.4 years, BMI: 27.3 +/- 0.45 Kg/m2, SBP: 140 +/- 26 mm Hg, DBP: 95.1 +/- 1.4 mm Hg. The fasting levels of glucose, insulin and lipids were measured in each individual. Both controls and patients were subjected to an oral glucose tolerance test (OGTT) with determination of glucose and insulin at 30, 60, and 120 minutes. The patients had significantly (p < 0.05) increased plasma glucose at 0, 30, 60 and 120 min. and increased (p < 0.05) plasma insulin levels at O and 120 min compared to controls. The G/I ratio was significantly lower (p < 0.005) in the hypertensive group, at 0 h and 120 min. Abnormalities in fasting lipid profile were also observed in the patients including a significant increase in TG, Cholesterol, VLDL-C and LDL-C. These increases were especially evident in men and those with higher BMI. There was a positive and significant association between basal-insulin and TG, VLDL-C and DBP in hypertensive patients. We conclude that hyperinsulinemia is present in the majority of hypertensive patients and that hyperinsulinemia is associated with lipid abnormalities specially in men and the most individuals with higher BMI.

[Metabolic changes associated with obesity in adults]. / Alteraciones metabólicas asociadas a la obesidad en adultos.

In order to find if the metabolic disorders more frequently found in our obese population were similar to the ones reported in the literature for other countries, a study was conducted in a group of 34 obese subjects (10 men and 24 women) whose only apparent alteration was a body mass index above 30 (mean value: 36.8 +/- 4.6) to obtain the relation between anthropometric measurements (Quetelet index, skinfold measures and waist/hip ratio) and plasma levels of nine biochemical parameters (including lipids, lipoproteins and glucose and insulin levels after an oral glucose load). The results revealed a tendency to the android distribution of fat in the female population, a significantly elevated triglyceride and total lipids levels and a decreased in HDL-cholesterol in both sexes. Hypercholesterolemia was present mainly in the male population. The most frequent dyslipidemia was Type IV (23%) followed by type IIb (15%). Practically none of the subjects had abnormal glycemic values after the glucose load, however the insulin levels were highly elevated in 80% of the patients, resulting in a great insulin/glucose ratios. Correlation analysis showed no association of the BMI with any biochemical parameter; only the insulin area was positively associated with anthropometric measures (mainly waist/hip ratio) and with the most altered biochemical parameter, the triglycerides. Variance analysis showed that only low HDL-cholesterol values were significantly different in patients presenting high blood pressure and familiar history of diabetes.

[Metabolic changes and most frequent complications in a group of type II diabetics. Their relation to the hyperglycemic state]. / Alteraciones metabólicas y complicaciones clínicas más frecuentes en un grupo de diabéticos tipo II. Su relación con el estado de hiperglicemia.

With the purpose of knowing which metabolic disorders and clinical complications are more frequently developed by diabetic patients, and to analyze the relationship between the hyperglycemia state and appearance of these complications, we studied a group of patients from a Metabolic Diseases Clinic in Maracaibo, Venezuela. Fifty-four Type II diabetics patients were evaluated by means of: physical examination, anthropometric measurements, biochemical control of glycemia, insulin and lipid pattern, as well as evaluation of the complications presented. The sample consisted of 33 men and 21 women, 75% of which had glycemic values over 140 mg/dl. Basal insulin values were significantly high (29.9 +/- 8.3 uU/ml in men and 30.9 +/- 10.1 uU/ml in women) in relation to a control group (14.5 +/- 2.4 uU/ml), concluding that our diabetics presented basal hyperinsulinemia and insulin resistance. The lipid pattern of the subjects studied showed hypertriglyceridemia (70%) and hypercholesterolemia (67%). A positive association between glycemia and triglycerides values was found in the total group. HDL-cholesterol values were significantly lower in relation to the control group, obtaining a negative correlation between HDL-cholesterol and triglycerides. The clinical complications observed in these diabetics were: non-specific visuals alterations, signs of arterial illness and sensorial disorders distributed in a similar percentage (63, 61 and 51%, respectively). When the independence test X2 was applied, we obtained association (p less than 0.05) between glycemia and the frequency of complications.

Sleep-dependent memory consolidation--what can be learnt from children?

Extensive research has been accumulated demonstrating that sleep is essential for processes of memory consolidation in adults. In children and infants, a great capacity to learn and to memorize coincides with longer and more intense sleep. Here, we review the available data on the influence of sleep on memory consolidation in healthy children and infants, as well as in children with attention-deficit/hyperactivity disorder (ADHD) as a model of prefrontal impairment, and consider possible mechanisms underlying age-dependent differences. Findings indicate a major role of slow wave sleep (SWS) for processes of memory consolidation during early development. Importantly, longer and deeper SWS during childhood appears to produce a distinctly superior strengthening of hippocampus-dependent declarative memories, but concurrently prevents an immediate benefit from sleep for procedural memories, as typically observed in adults. Studies of ADHD children point toward an essential contribution of prefrontal cortex to the preferential consolidation of declarative memory during SWS. Developmental studies of sleep represent a particularly promising approach for characterizing the supra-ordinate control of memory consolidation during sleep by prefrontal-hippocampal circuitry underlying the encoding of declarative memory.