Verification Study of In Silico Computed Intracardiac Blood Flow With 4D Flow MRI.

OBJECTIVE: Major challenges for clinical applications of in silico medicine are limitations in time and computational resources. Computational approaches should therefore be tailored to specific applications with relatively low complexity and must be verified and validated against clinical gold standards. METHODS: This study performed computational fluid dynamics simulations of left ventricular hemodynamics of different complexity based on shape reconstruction from steady state gradient echo magnetic resonance imaging (MRI) data. Computed flow results of a rigid wall model (RWM) and a prescribed motion fluid-structure interaction (PM-FSI) model were compared against phase-contrast MRI measurements for three healthy subjects. RESULTS: Extracted boundary conditions from the steady state MRI sequences as well as computed metrics, such as flow rate, valve velocities, and kinetic energy show good agreement with in vivo flow measurements. Regional flow analysis reveals larger differences. CONCLUSION: Basic flow structures are well captured with RWM and PM-FSI. For the computation of further biomarkers like washout or flow efficiency, usage of PM-FSI is required. Regarding boundary-near flow, more accurate anatomical models are inevitable. SIGNIFICANCE: These results delineate areas of application of both methods and lay a foundation for larger validation studies and sensitivity analysis for healthy and diseased cases, being an essential step upon clinical translations.

The German Three Factor Impulsivity Index: Confirmatory factor analysis and ties to demographic and health-related variables.

A growing body of research has focused on the differentiation of emotion-related versus non-emotion-related impulsivity, assessed by the Three-Factor Impulsivity (TFI) index. The goal of this study is to develop a German TFI index, and to validate the emotion-related impulsivity subscales against indices of substance abuse, physical or psychological disorder, physical exercise, BMI, and hours of sleep. 395 native-German speakers completed the German TFI index and questions on validity indicators online. Factor analyses supported the three-factor structure, including Pervasive Influence of Feelings, Lack of Follow Through, and Feelings Trigger Action. Correlations between factors were higher than in the original work. Both emotion-related impulsivity subscales correlated significantly with psychological disorder, engagement in and minutes of physical exercise per week. When included in multivariate regression models, the three factors explained 3.1%, and 29.2% of variance in amount of exercise per week and psychological disorder, respectively. In sum, findings indicated that the German TFI index has a robust three-factor structure that showed expected links to validity indicators, and novel effects in relation to physical exercise.

Efficacy, acceptability, and tolerability of all available treatments for insomnia in the elderly: a systematic review and network meta-analysis.

OBJECTIVES: Symptoms of insomnia are highly prevalent in the elderly. A significant number of pharmacological and non-pharmacological interventions exist, but, up-to-date, their comparative efficacy and safety has not been sufficiently assessed. METHODS: We integrated the randomized evidence from every available treatment for insomnia in the elderly (>65 years) by performing a network meta-analysis. Several electronic databases were searched up to May 25, 2019. The two primary outcomes were total sleep time and sleep quality. Data for other 6 efficacy and 8 safety outcomes were also analyzed. RESULTS: Fifty-three RCTs with 6832 participants (75 years old on average) were included, 43 of which examined the efficacy of one or more drugs. Ten RCTs examined the efficacy of non-pharmacological interventions and were evaluated only with pairwise meta-analyses because they were disconnected from the network. The overall confidence in the evidence was very low primarily due to the small amount of data per comparison and their sparse connectedness. Several benzodiazepines, antidepressants, and z-drugs performed better in both primary outcomes, but few comparisons had data from more than one trial. The limited evidence on non-pharmacological interventions suggested that acupressure, auricular acupuncture, mindfulness-based stress reduction program, and tart cherry juice were better than their control interventions. Regarding safety, no clear differences were detected among interventions due to large uncertainty. CONCLUSIONS: Insufficient evidence exists on which intervention is more efficacious for elderly patients with insomnia. More RCTs, with longer duration, making more direct interventions among active treatments and presenting more outcomes are urgently needed.

Choroid Plexus Cyst in a Neonatal Burmeister's Porpoise (Phocoena spinipinnis).

Neuroectodermal developmental anomalies are reported rarely in cetaceans and central nervous system cysts are not described. We describe the gross, microscopical, histochemical and immunohistochemical features of a neuraxial myelencephalic cyst in a stranded neonatal Burmeister's porpoise (Phocoena spinipinnis). Grossly, a subdural, extra-axial, well-demarcated, yellow fluid-filled cystic structure (1.9 × 1.6 × 1 cm) expanded the left foramen of Luschka, the left caudolateral cerebellar recess and the left cranioventral myelencephalon. The cyst displaced the ipsilateral ventral paraflocculus and distended the underlying cranial nerves IX, X, XI and XII. Microscopically, the cystic structure was lined by a monolayer of low cuboidal to flattened epithelium supported by a thin fibrovascular matrix. Immunohistochemistry (IHC) revealed strong and diffuse expression of AE1/AE3 and focal positivity for vimentin. IHC for epithelial membrane antigen, glial fibrillary acid protein, synaptophysin and S100 was negative. Based on these findings, an extra-axial cyst of the choroid plexus of the fourth ventricle (CCPFV) was diagnosed. The pathological relevance of the CCPFV in this case is uncertain. The cause of death involved severe perinatal interspecific (shark) trauma. The present case provides the first evidence of a neuroepithelial cyst in cetacean species.

Choroid Plexus Cyst in a Neonatal Burmeister's Porpoise (Phocoena spinipinnis)

Neuroectodermal developmental anomalies are reported rarely in cetaceans and central nervous system cysts are not described. We describe the gross, microscopical, histochemical and immunohistochemical features of a neuraxial myelencephalic cyst in a stranded neonatal Burmeister's porpoise (Phocoena spinipinnis). Grossly, a subdural, extra-axial, well-demarcated, yellow fluid-filled cystic structure (1.9 × 1.6 × 1 cm) expanded the left foramen of Luschka, the left caudolateral cerebellar recess and the left cranioventral myelencephalon. The cyst displaced the ipsilateral ventral paraflocculus and distended the underlying cranial nerves IX, X, XI and XII. Microscopically, the cystic structure was lined by a monolayer of low cuboidal to flattened epithelium supported by a thin fibrovascular matrix. Immunohistochemistry (IHC) revealed strong and diffuse expression of AE1/AE3 and focal positivity for vimentin. IHC for epithelial membrane antigen, glial fibrillary acid protein, synaptophysin and S100 was negative. Based on these findings, an extra-axial cyst of the choroid plexus of the fourth ventricle (CCPFV) was diagnosed. The pathological relevance of the CCPFV in this case is uncertain. The cause of death involved severe perinatal interspecific (shark) trauma. The present case provides the first evidence of a neuroepithelial cyst in cetacean species.

anomalias de desenvolvimento neuroectodérmicas são raramente relatadas em cetáceos e cistos do sistema nervoso central não são descritos. Descrevemos as características macroscópicas, microscópicas, histoquímicas e imuno-histoquímicas de um cisto mielencefálico neuroaxial em uma toninha de Burmeister neonatal encalhada (Phocoena spinipinnis). Grosso modo, uma estrutura cística amarela subdural, extra-axial, bem demarcada e cheia de líquido (1,9 × 1,6 × 1 cm) expandiu o forame esquerdo de Luschka, o recesso cerebelar caudolateral esquerdo e o mielencéfalo cranioventral esquerdo. O cisto deslocou o paraflóculo ventral ipsilateral e distendeu os nervos cranianos subjacentes IX, X, XI e XII. Microscopicamente, a estrutura cística foi revestida por uma monocamada de epitélio cubóide a achatado baixo, suportada por uma fina matriz fibrovascular. A imuno-histoquímica (IHC) revelou forte e difusa expressão de AE1 / AE3 e positividade focal para vimentina. O IHC para antígeno da membrana epitelial, proteína do ácido fibrilar glial, sinafofisina e S100 foi negativo. Com base nesses achados, foi diagnosticado um cisto extra-axial do plexo coróide do quarto ventrículo (CCPFV). A relevância patológica do CCPFV neste caso é incerta. A causa da morte envolveu traumatismo interespecífico (tubarão) perinatal grave. O presente caso fornece a primeira evidência de um cisto neuroepitelial em espécies de cetáceos. patologia cetáceo Anomalia congenita neuroectoderma

Agomelatine improves sleep in a patient with fatal familial insomnia.

A young patient with FFI was started on agomelatine 25 mg to medicate nocturnal insomnia. Under this treatment sleep efficiency was improved, slow wave sleep was high and awakenings during sleep period time were far less than before. Clinically the patient was less restless during nighttime.

Maternal influences on thiamine status of walleye Sander vitreus ova.

Concentrations of the various forms of thiamine (vitamin B(1) ) were determined in walleye Sander vitreus ova from three central North American lakes. Total thiamine concentrations in ova from Lake Winnipeg S. vitreus were approximately three times greater (mean 12 nmol g(-1) ) than in those from Lakes Erie or Ontario. The percentage of thiamine in the active form (thiamine pyrophosphate, TPP) was highest in Lake Ontario ova (mean 88%) and lowest in those from Lake Winnipeg (mean 70%). Neither ova total thiamine concentration nor per cent ova thiamine as TPP showed any consistent relationships with maternal age, size, morphometric condition, somatic lipid concentrations or liver lipid concentrations. Ova total thiamine concentration, however, was negatively related to ovum size in some populations, as well as among populations, and was positively related to liver total thiamine concentration. Maternal transfer of thiamine to ova appears to be independent of female ontogenetic or conditional state in S. vitreus.

Motor activity in depressed patients during therapeutic sleep deprivation.

PROBLEM: Both sleep and motor activity have a bidirectional relationship with depression. The existing literature on motor activity during therapeutic sleep deprivation in depressed patients is inconsistent and fragmentary. In the present study we measured motor activity continuously during 40 hours of sleep deprivation in depressed patients. METHOD: Thirty-four inpatients suffering from a major depression (DSM-IV) underwent sleep deprivation with a continuous waking period of 40 hours. Motor activity of the patients was continuously recorded using an actigraph on the non-dominant wrist. The effect of sleep deprivation was assessed by the Hamilton Depression Scale (six-item version), thus separating the group into responders and non-responders to sleep deprivation. RESULTS: We found no significant differences in motor activity between responders and non-responders on the day before sleep deprivation. During the night, responders to sleep deprivation exhibited a higher motor activity and less periods of rest. On the day after sleep deprivation, responders exhibited a higher activity, too. CONCLUSIONS: Motor activity levels differ between the two groups, thus giving more insight into possible mechanisms of action of the therapeutic sleep deprivation. We suggest that higher motor activity during the night prevents naps and leads to better response to sleep deprivation.

[Basic diagnostics of sleep disorders: possibilities of the family physician]. / Basisdiagnostik der Schlafstörungen. Schlüsselrolle für den Hausarzt.

Many sleep disorders can be definitively diagnosed using basic diagnostics in the family practice. Important elements of the diagnosis are the patient's general medical history and acquiring a description of the current phenomenology of the disorder. The use of sleep diaries and information provided by a third party are also helpful. For chronic sleep disorders, patient habits that are not in line with the rules of good sleep hygiene should be regarded as potential perpetuating causes of the disorder. In some cases, simple test procedures can also be useful. The identification or the exclusion of a primary physical or mental disease whose symptom may be the sleep disorder (example: insomnia for underlying depression) is important. In some cases, referral to a specialist or to a sleep medicine centre is necessary.

[Drug treatment of sleep disorders in the elderly]. / Arzneimittelbehandlung von Schlafstörungen im Alter.

Changes in the pattern of sleep, e.g. more frequent nocturnal awakenings, are normal in the elderly. There is also a greater incidence of medical and psychiatric sleep disorders (depression, dementia). Initially, a thorough diagnostic assessment should be performed in order to identify disorders which can be treated specifically. For the symptomatic drug treatment of insomnias, the specific metabolic and pharmacokinetic, as well as possible interactions, should be considered. The new benzodiazepine receptor agonists (zopiclone, zolpidem and zaleplone), with their favourable risk-benefit profile, can be considered as first-choice treatments in elderly patients; in general, they should be preferred to the classical benzodiazepines. When a longer treatment is necessary, certain (non-anticholinergic) antidepressants and neuroleptics can be considered (the latter especially in cases of abnormal nocturnal behaviour). Herbal drugs and other hypnotically active compounds play a secondary role. Drug treatment of insomnia should always be carried out in the context of a general treatment plan which also includes non-pharmacological elements. In elderly patients, "chronotherapeutic" methods, which accentuate the sleep-wake rhythm, are of crucial importance.

Is the antidepressive effect of sleep deprivation stabilized by a three day phase advance of the sleep period? A pilot study.

Sleep deprivation (SD) induces a rapid amelioration of mood in about 60 % of depressed patients. After the next night of sleep, however, most patients experience a relapse. Previous studies demonstrated that a six day sleep-phase advance protocol prevents relapses in about 60 % of patients who responded positively to SD. We investigated whether also a three day phase advance of the sleep period might be able to maintain the antidepressant effects of SD. Twenty-eight medicated depressed inpatients, who had a significant improvement after a SD in one night were recruited for this study. The phase advance protocol began on the first day after SD with a bed time from 5:00 p. m. to 12:00 p. m. on the first, from 7:00 p. m. to 2:00 a. m. on the second and 9:00 p. m. to 4:00 a. m. on the third day after SD. Three patients dropped out because of protocol violations. Only ten of the remaining 25 SD responders had a relapse during the three days of phase advance treatment or during the two days after it. Two of the relapsers improved again until day 6, i. e. 68 % showed an improvement of at least 30 % six days after the beginning of the treatment. This study indicates that even a three day phase advance protocol may help to prevent relapses after successful SD.

Trimipramine in primary insomnia: results of a polysomnographic double-blind controlled study.

In recent years, sedating antidepressants have been increasingly used to treat primary insomnia. Up to now, only one open pilot study with trimipramine and one double-blind placebo-controlled study with doxepin have provided scientific support for this approach in treating primary insomnia. In order to test the hypothesis that sedating antidepressants are useful in the treatment of primary insomnia, the effect of trimipramine on objectively and subjectively measured parameters of sleep was investigated in a double-blind placebo- and lormetazepam-controlled study in a sample of 55 patients with primary insomnia attending outpatient sleep-disorder clinics. Trimipramine was selected since it has shown positive effects on sleep continuity with a lack of REM sleep suppression in studies on depressed patients and in one pilot study on patients with primary insomnia. Trimipramine at an average dose of 100 mg over a period of 4 weeks significantly enhanced sleep efficiency, but not total sleep time (which had been the primary target variable) compared to placebo as measured by polysomnography. Changes in objective sleep parameters were paralleled by changes in subjective sleep parameters. Trimipramine did not suppress REM sleep. Lormetazepam decreased wake time and sleep stage 3 and increased REM sleep compared to placebo. After switching trimipramine to placebo, sleep parameters returned to baseline. There was no evidence of any rebound effect from trimipramine. Side effects from trimipramine were only marginal. This first double-blind placebo-controlled study with trimipramine suggests its efficacy in the treatment of primary insomnia. However, due to the large intra- and interindividual variance in the parameters of interest before and during treatment a larger sample size would have been necessary to strengthen the validity of our findings.

Sleep and sleep-wake cycle in an 81-year-old patient with de novo ultra-rapid cycling bipolar disorder.

This is a case report of an 81-year-old man who developed de novo bipolar disorder with ultrarapid cycling at the age of 80. Mood was self-rated daily over a period of ten weeks; in addition, polysomnographic and motor activity recordings were performed during a drug-free baseline period. Both depressive and hypomanic episodes had an average duration of about 30 hours; the affective cycle was thus independent from the sleep-wake cycle. When mood shifts occurred during nighttime, sleep was different in nights following depression than in nights following hypomania. Positron emission tomography revealed a moderate bilateral frontal hypermetabolism in the hypomanic phase and yielded normal findings for the depressive stage. In contrast to what is usually expected in ultra-rapid cycling bipolar disorder, this case demonstrates an unusual sleep-unrelated cycle duration in the oldest reported patient so far.

Patterns of response to repeated total sleep deprivations in depression.

BACKGROUND: Patterns of response and nonresponse in repeated sleep deprivation (SD) are of both clinical and scientific interest; as yet, studies have yielded inconsistent results. METHODS: Eighteen inpatients suffering from a major depression were subjected to a series of six scheduled total sleep deprivations within 3 weeks; 12 of them completed the whole protocol. All were under a constant antidepressant medication with amitriptyline. SD effects were measured using observer and self rating scales. RESULTS: Each single SD led to a significant improvement. Of the 12 patients who completed the protocol, seven were classified as responders at endpoint (i.e., 1 week after the sixth TSD). The majority of patients exhibited a pattern of responses and nonresponses randomly distributed over time. There was no temporal trend. The initial effect did not predict the average response to the following SDs. LIMITATIONS: One third of patients dropped out before completing the protocol which limits the scope of the study. CONCLUSIONS: Response to a single SD is not generalizable on a series of following SDs in an individual. The mechanism of action of SD does probably not involve mechanisms subjected to habituation or sensitization.

Transmission line probe based on a bow-tie antenna.

A high transmission probe for scanning near-field optical microscopy is discussed that is based on a bow-tie antenna. The proposed design of the transmission line probe relies on batch-fabricated hollow pyramidal silicon dioxide tips that are partly coated with aluminium to accomplish the tapered dipole antenna. Theoretical calculations of the field distribution were performed to investigate its optical properties. Results were compared with those of conventional aperture tips based on the same silicon dioxide tip configuration, and revealed unique properties with respect to the transmission efficiency.

[Effectiveness of zopiclone in disorders of initiating and maintaining sleep. Results of a drug monitoring study in 811 general practices]. / Die Effektivität von Zopiclon bei Ein- und Durchschlafstörungen. Ergebnisse einer Anwendungsbeobachtung in 811 Hausarztpraxen.

BACKGROUND AND METHOD: In a drug monitoring study with 811 participating general practitioners, safety and tolerability of zopiclone were studied in 2416 patients with disorders of initiating and maintaining sleep. RESULTS: In general, zopiclone was efficient in all forms of insomnia; the subjective sleep duration was prolonged for 2 hours on average. Patients without somatic complaints or comorbidity showed the greatest benefit. Daytime well-being and vigilance were in general not impaired. Drug related adverse events occurred rarely; the great majority of the participating physicians rated the treatment with zopiclone as efficient and acceptable. CONCLUSION: In this drug monitoring study, zopiclone proved an efficient hypnotic for the treatment of disorders of initiating and maintaining sleep.

[Kufs-disease; a rare cause of early-onset dementia]. / Die Kufs-Erkrankung. Seltene Ursache einer früh beginnenden Demenz.

The case of a 35-year-old man with progressive dementia from the age of 17 is presented. Clinical examination showed mild extrapyramidal and cerebellar signs and rare myoclonus. Neuropsychological evaluation disclosed severe cognitive deficits. Magnetic resonance imaging (MRI) revealed moderate generalized atrophy with abnormal iron deposition in the basal ganglia. Positron emission tomography (PET) with 18-fluorodeoxyglucose (18-FDG) demonstrated clear temporoparietal hypometabolism. The clinical symptoms and course are typical for the rare adult type of neuronal ceroid lipofuscinoses (Kufs' disease). The diagnosis is supported by the electron microscope detection of an abnormal accumulation of lipid vacuoles and lipofuscin in the eccrine sweat glands and the rectal ganglia cells.

Prediction of antidepressant effects of sleep deprivation by metabolic rates in the ventral anterior cingulate and medial prefrontal cortex.

OBJECTIVE: Sleep deprivation has been shown to have an antidepressant benefit in a subgroup of depressed patients. Functional imaging studies by the authors and others have suggested that patients with elevated metabolic rates in the anterior cingulate gyrus at baseline are more likely to respond to either sleep deprivation or antidepressant medications than patients with normal metabolic rates. The authors extend their earlier work in a larger group of patients and explore additional brain areas with statistical probability mapping. METHOD: Thirty-six patients with unipolar depression and 26 normal volunteers were studied with positron emission tomography before and after sleep deprivation. Response to sleep deprivation was defined as a 40% or larger decrease in total scores on the Hamilton Depression Rating Scale. RESULTS: One-third of the depressed patients had a significant response to sleep deprivation. Responders had higher relative metabolic rates in the medial prefrontal cortex, ventral anterior cingulate, and posterior subcallosal gyrus at baseline than depressed patients who did not respond to sleep deprivation and normal volunteers. Lower Hamilton depression scores correlated significantly with lower metabolic rates in the left medial prefrontal cortex. After sleep deprivation, significant decreases in metabolic rates occurred in the medial prefrontal cortex and frontal pole in the patients who responded positively to sleep deprivation. CONCLUSIONS: High pretreatment metabolic rates and decreases in metabolic rates after treatment in the medial prefrontal cortex may characterize a subgroup of depressed patients who improve following sleep deprivation and, perhaps, other antidepressant treatments.