Relationship between Contingent Negative Variation and afterimage duration in migraine patients.

Background: Abnormalities in electrocortical parameters and persistence of afterimage after visual stimulation are known to occur in migraine patients. The results of studies on Contingent Negative Variation (CNV) and afterimage persistence in migraine patients suggest a link between these two phenomena and a connection to the pathomechanism of migraine. Objectives: To date, no studies have investigated both afterimage duration and CNV parameters in the same subjects. The aim of this study was to investigate the relationship between the early component of CNV (iCNV) and the duration of the afterimage in migraine patients. Methods: Sixty seven migraine patients from the headache center of the University of Rostock Medical Center were examined for iCNV amplitude, iCNV habituation and afterimage duration. The subjects also completed questionnaires developed for this study and the MIDAS (Migraine Disability Assessment) questionnaire. Results: Associations were found between iCNV amplitude and afterimage duration and between habituation capacity and afterimage duration. A deficit in habituation capacity correlated with a significantly prolonged afterimage duration. Increased iCNV amplitude and prolonged afterimage duration were also significantly correlated. Conclusion: Conclusions about the pathophysiology of migraine can be drawn from the results of this study. The results support the hypothesis of cortical hyperexcitability as a consequence of a low pre-activation level, which may be a possible contributory cause of migraine. Furthermore, they allow assessment of whether the afterimage examination, which is easier and quicker to perform than the CNV examination, can be used as a diagnostic tool or as a parameter to monitor the course of therapy in people with migraine.

Comparison of empathy profiles of medical students at the start and in the advanced clinical phase of their training.

Background: The National Competence Based Catalogue of Learning Objectives for Undergraduate Medical Education (NKLM) cites empathy as a basic competence for medical doctors. Based on a multidimensional concept of clinical empathy, empathy profiles of medical students at the start of their training and in the 9th semester were identified and compared in order to draw conclusions for the conception of effective course offers. Method: Using the Saarbrücker Personality Questionnaire on Empathy (SPF-IRI), self-rated empathy was recorded in a cross-sectional study of medical students (1st semester: N=192/9th semester: N=221). Two Stage Clustering was performed for data analysis. Result: Three empathy profiles which could be meaningfully delineated by content were identified: 1. reflected, functional empathy, 2. unreflected, burdensome empathy and 3. distancing and avoidance. Students in the 9th semester mostly tended toward unreflected, burdensome empathy. Only one-third appeared capable of feeling empathy with patients while at the same time adequately regulating their own emotions and thus protecting themselves from emotional overload. Conclusion: An adequately reflected and functional empathy among medical students can neither be assumed at the start of their training, nor do existing course offers appear to provide sufficient training for this. Empathy should thus be implemented as a competence which needs to be promoted over the entire course of study. Emotion regulation plays a key role.

Efficacy of cranial electrotherapy stimulation in patients with burning mouth syndrome: a randomized, controlled, double-blind pilot study.

Background: The Burning mouth syndrome (BMS) is a chronic pain syndrome characterized by a burning sensation in the oral mucous membranes. The etiology and pathophysiology of BMS is largely unexplained. To date, there is no evidence-based treatment strategy for BMS. Cranial electrical stimulation (CES) represents a non-invasive treatment option with a low side effect profile that is approved for the treatment of pain, depression, anxiety disorder and insomnia. It has shown efficacy in studies for chronic pain such as fibromyalgia and neuropathic pain after spinal cord injury. This study aimed to investigate the therapeutic effectiveness of CES in combination with local transcutaneous electrical nerve stimulation (TENS) as an adjunct therapy in patients with BMS compared to sham stimulation. Methods: This randomized, double-blind, sham-controlled pilot study enrolled 22 patients, aged 18 years and over, with the diagnosis of BMS meeting the ICHD-3 criteria from August 2020 to June 2021. The study duration was 4 weeks (28 days) per participant. After randomization, the active group participants (n = 11) received a 100 µA CES treatment for 60 min a day whereas the devices in the Sham group did not emit electricity. Simple linear regression was used to determine whether the interventions promoted significant differences in pain intensity. Results: The linear regression showed that the period of stimulation significantly predicted decrease in the intensity of pain in the active group [ß = -0.036; t(26) = -7.219; p < 0.001] as in the sham group [ß = -0.026; t(26) = -2.56; p < 0.017]. With the applied cutoff of 30% pain reduction within the stimulation period, both the active and sham groups had 36% responders (n = 4) (Fisher's exact test, p = 1.00). In both groups (active stimulation and sham group), a significant decrease in the intensity of pain, somatic symptoms and an improvement in sleep quality over the study period was observed. Subjects reported no adverse events during the study. Conclusion: Although CES is an easily applicable and safe therapeutic option for chronic facial pain, active stimulation was not superior to sham stimulation. Among other reasons, this could be due to the short double-blinded treatment period, duration of the daily stimulation session or the small sample size.

[Interdisciplinary multimodal pain therapy in headache disorders]. / Interdisziplinäre multimodale Schmerztherapie bei Kopfschmerzerkrankungen.

Primary headaches are among the most common pain disorders. They include migraines (prevalence 15%), tension headaches (up to 80%), and others, including trigeminal autonomic headaches (about 0.2%). Migraine, in particular, leads to significant impairment of personal life and high societal costs. Therefore, the need for effective and sustainable therapeutic procedures is high. This article provides an overview of psychological procedures in headache therapy and critically summarizes the empirical evidence for the effectiveness of interdisciplinary multimodal pain therapy (IMST) consisting of psychotherapy and pharmacotherapy. It can be shown that psychoeducation, relaxation procedures, cognitive behavioral therapy, and biofeedback are psychological procedures from which headache patients can benefit. In the synopsis of multimodal approaches in the treatment of headache, consistently greater effects can be observed when both pharmacological treatment and psychotherapeutic procedures are used. This added value should be regularly taken into account in the treatment of headache disorders. This requires close cooperation between headache specialists and psychotherapists who specialize in the treatment of pain.

Headache impact and socioeconomic status: findings from a study of the German Migraine and Headache Society (DMKG).

BACKGOUND: Headache disorders are not only among the most prevalent, they are also among the most disabling disorders worldwide. This paper investigates the association between headache impact on daily life and the socioeconomic status (SES) of headache sufferers. METHODS: Data stem from a random general population sample in Germany. Respondents who reported having headache for at least a year and were aged ≥ 18 years were included in the study. A standardized questionnaire addressing headache and headache treatment was filled in during the face-to-face survey. The impact of headache on daily life was measured using the German version of the Headache Impact Test (HIT-6). RESULTS: Higher headache impact was found in low and medium SES compared to high SES. After adjustment for sociodemographics, headache-related factors (analgesic use, headache duration, headache frequency, migraine diagnosis), depressive symptoms, physical inactivity and obesity, an increased odds ratio of having higher headache impact in low SES compared to high SES was found: OR = 1.83, 95% CI [1.43, 2.23], p = .014. When the interactions "SES*obesity", "SES*depressive symptoms", and "SES*physical inactivity" were added, the results showed a significant interaction effect of "SES*obesity". Obese persons with low SES were 3.64 times more likely to have higher headache impact than non-obese persons with low SES. No significant differences between obese and non-obese persons were found in the medium and high SES groups. CONCLUSIONS: SES is an important factor that should not be neglected in headache awareness campaigns and headache treatment. Longitudinal studies are needed in the future to investigate whether lifestyle interventions, such as weight reduction, can help to reduce headache impact in people in lower SES.

Social inequality, social networks, and health: a scoping review of research on health inequalities from a social network perspective.

BACKGROUND: This review summarises the present state of research on health inequalities using a social network perspective, and it explores the available studies examining the interrelations of social inequality, social networks, and health. METHODS: Using the strategy of a scoping review, as outlined by Arksey and O'Malley (Int J Sci Res Methodol 8:19-32, 2005), our team performed two searches across eight scientific, bibliographic databases including papers published until October 2021. Studies meeting pre-defined eligibility criteria were selected. The data were charted in a table, and then collated, summarised, and reported in this paper. RESULTS: Our search provided a total of 15,237 initial hits. After deduplication (n = 6,168 studies) and the removal of hits that did not meet our baseline criteria (n = 8,767 studies), the remaining 302 full text articles were examined. This resulted in 25 articles being included in the present review, many of which focused on moderating or mediating network effects. Such effects were found in the majority of these studies, but not in all. Social networks were found to buffer the harsher effects of poverty on health, while specific network characteristics were shown to intensify or attenuate the health effects of social inequalities. CONCLUSIONS: Our review showed that the variables used for measuring health and social networks differed considerably across the selected studies. Thus, our attempt to establish a consensus of opinion across the included studies was not successful. Nevertheless, the usefulness of social network analysis in researching health inequalities and the employment of health-promoting interventions focusing on social relations was generally acknowledged in the studies. We close by suggesting ways to advance the research methodology, and argue for a greater orientation on theoretical models. We also call for the increased use of structural measures; the inclusion of measures on negative ties and interactions; and the use of more complex study designs, such as mixed-methods and longitudinal studies.

Medication adherence in patients with cluster headache and migraine: an online survey.

To examine factors for adherent and non-adherent behavior in patients with cluster headache and migraine. Adults with cluster headache or migraine were included in this anonymous online survey using a questionnaire accessed via homepages of headache support groups. Medication adherence in preventive treatment was measured with the Medication Adherence Report Scale (MARS-D). Factors for non-adherent behavior were examined (subjective socioeconomic status, psychological comorbidities, self-efficacy, coping, side effects, expectations of treatment, information on medical treatment, and trust in the physician/treatment concept). 200 participants (n = 58 with cluster headache, n = 142 with migraine) were included. The rate of medication adherence in preventive treatment was 32.8% for participants with cluster headache and 20.4% for migraine. The most common reasons for low adherence in participants with cluster headache were altering the prescribed medication dose (34%) or taking less than instructed (14%), which was mostly due to insufficient benefit from the medication or side effects. Positive expectations of medical treatment (p ≤ 0.05) correlated significantly with adherent behavior in cluster headache. Furthermore, the adherence-promoting factors coping and self-efficacy were more pronounced in patients with cluster headache than in those with migraine (p < 0.05). This study is the first to comprehensively investigate medication adherence and factors influencing adherent/non-adherent behavior in patients with cluster headache. Patients with cluster headache had similar adherence levels to patients with migraine, but had higher resources of adherence-promoting factors.

Immune checkpoint inhibition and targeted therapy for melanoma: A patient-oriented cross-sectional comparative multicentre study.

BACKGROUND: Choosing the adequate systemic treatment for melanoma is driven by clinical parameters and personal preferences. OBJECTIVE: Evaluation of the impact of disease and treatment on the daily life of patients receiving systemic therapy for melanoma. METHODS: A German-wide, cross-sectional comparative study was conducted at 13 specialized skin cancer centres from 08/2020 to 03/2021. A questionnaire was distributed to assess patients' perception of disease and symptoms, the impact of their current treatment on quality of life (QOL) and activities, adverse events (AEs), therapeutic visits, as well as believe in and satisfaction with their current systemic melanoma treatment. Patient-reported outcomes (PROs) were rated on a continuous numerical rating scale or selected from a given list. RESULTS: Four hundred and fourteen patients with systemic melanoma therapy were included. 359 (87%) received immune checkpoint inhibition (ICI) and 55 (13%) targeted therapy (TT). About 1/3 of patients were adjuvantly treated, the remaining because of unresectable/metastatic melanoma. In subgroup analyses, only in the adjuvant setting, TT patients reported a significant decrease in their treatment associated QOL compared to patients with ICI (p = 0.02). Patients with TT were 1.9 times more likely to report AEs than patients with ICI, a difference being significant just for the adjuvant setting (p = 0.01). ICI treatment intervals differed significantly between adjuvant and unresectable/metastatic setting (p = 0.04), though all patients, regardless of their specific ICI drug, evaluated their treatment frequency as adequate. TT patients with dabrafenib/trametinib (n = 37) or encorafenib/binimetinib (n = 15) did not differ regarding the strain of daily pill intake. Patients older than 63 years rated various PROs better than younger patients. CONCLUSIONS: Patients evaluated their treatment mainly positively. ICI might be preferred over TT regarding QOL and patient-reported AEs in the adjuvant setting. Older melanoma patients appeared to be less impacted by their disease and more satisfied with their treatment.

Promoting rational antibiotic therapy among high antibiotic prescribers in German primary care-study protocol of the ElektRA 4-arm cluster-randomized controlled trial.

BACKGROUND: The rational use of antibiotics is of great importance in health care. In primary care, acute respiratory infections are the most common cause of inappropriate antibiotic prescribing. Since existing studies aiming to optimize antibiotic use are usually based on the voluntary participation of physicians, general practitioners (GPs) with inappropriate prescribing behavior are underrepresented. For the first time in Germany, the ElektRA study will assess and compare the effects of three interventions on antibiotic prescribing rates for respiratory and urinary tract infections among high prescribers in primary care. METHOD: ElektRA is a 4-arm cluster-randomized controlled trial among German GPs in nine regional Associations of Statutory Health Insurance Physicians. On their behalf, the Central Research Institute of Ambulatory Health Care in Germany (Zi) analyses all outpatient claims and prescription data. Based on this database, high antibiotic prescribing GPs are identified and randomized into four groups: a control group (N=2000) and three intervention arms. We test social norm feedback on antibiotic prescribing (N=2000), social norm feedback plus online training on rational prescribing practice and communication strategies (N=2000), and social norm feedback plus online peer-moderated training on rational antibiotic prescribing, communication strategies, and sustainable behavior change (N=1250). The primary outcome is the overall rate of antibiotic prescriptions. Outcomes are measured before intervention (T0, October 2020-September 2022) and over a period of 15 months (T1, October 2022 to December 2023) after randomization. DISCUSSION: The aim of the study is to implement individualized, low-threshold interventions to reduce antibiotic prescribing among high prescribers in primary care. If successful, a change in behavior among otherwise difficult-to-reach high prescribers will directly improve patient care. The increase in quality of care will ideally be achieved both in terms of the quantity of antibiotics used as well as the kind of substances prescribed. Also, if effective strategies for high prescribers are identified through this study, they can be applied not only to the antibiotics addressed in this study, but also to other areas of prescription management. TRIAL REGISTRATION: Current Controlled Trials ISRCTN95468513.

Physical Activity is Associated with Less Analgesic Use in Women Reporting Headache-A Cross-Sectional Study of the German Migraine and Headache Society (DMKG).

INTRODUCTION: The aim of this analysis is to determine whether regular physical activity is associated with less analgesic use in men and women suffering from headache disorders based on population-based cross-sectional data. METHODS: We used data from a random general population sample in Germany that comprised 2477 participants aged ≥ 14 years. A standardized questionnaire addressing headache and headache treatment was filled in during the face-to-face survey. RESULTS: Thirty-nine percent of the participants reported headache. Of these, 37.5% of men and 33.6% of women were physically active. Of the participants with headache, 43.3% reported taking analgesics on < 2 days a month, 40.7% on 2-5 days a month, 10.1% on 6-10 days a month, and 5.9% on > 10 days a month. Frequent headache, severe impact of headache on daily life, and depressive symptoms were associated with higher analgesic use in both men and women. For women, physical inactivity was associated with the frequency of analgesic use adjusted for sociodemographic and headache-related variables. For men, results did not suggest any association between physical inactivity and frequency of analgesic use. CONCLUSIONS: There are both sex-unspecific and sex-specific factors associated with analgesic use among men and women with headache. In women with increased analgesic use, promoting physical activity may reduce analgesic use. For men, education about the therapeutic effects of physical activity for headaches is an important resource.

Types of leisure time physical activities (LTPA) of community-dwelling persons who have been screened positive for dementia.

BACKGROUND: To (a) describe the pattern of leisure time physical activities (LTPA) in community-dwelling persons who have been screened positive for dementia and (b) determine the health-related and sociodemographic factors associated with LTPA. METHODS: Data of the general practitioner-based, randomized, controlled intervention trial, DelpHi-MV (Dementia: life- and person-centered help in Mecklenburg-Western Pomerania) were used. Patients aged 70 years or older, who lived at home and had a DemTect< 9 were informed about the study by their General practitioners and invited to participate. Data from 436 participants with complete baseline data were used. Standardized, computer-assisted assessments were made during face-to-face interviews at the participants' homes. RESULTS: Two hundred thirty-eight patients (54.6%) carried out LTPA (men 58.4%, women 51.8%). Physically active patients mentioned one to two different activities; diversity of LTPA was higher for men than for women. The most-frequently mentioned types of activity were gardening (35.3%), cycling (24.1%) and mobility training (12.4%); there was only a statistically significant difference between men and women in cycling, χ2(1) = 21.47, p < .001. The odds of LTPA increased with increasing quality of life (OR = 2.41), lower impairments in activities of daily living (OR = 0.85), and living in a rural environment (OR = 2.02). CONCLUSIONS: Our findings suggest that people who have been screened positive for dementia living in a rural area are more likely to be active than people living in an urban area. Following studies should investigate whether this difference has an effect on the progression of dementia. TRIAL REGISTRATION: ClinicalTrial.gov Identifier NCT01401582 .

Use of outpatient medical care by headache patients in Germany: a population-based cross-sectional study.

BACKGROUND: Headache sufferers in need of professional health care often do not utilize the care available, and factors influencing headache-specific physician consultation are not yet understood. Objectives of this study are (1) to assess self-reported headache-specific physician consultations and (2) to identify headache-related and sociodemographic predictors. METHODS: Data of a random sample of the general population in Germany aged ≥14 years were analyzed (N = 2461). A multivariate binary logistic regression was conducted to identify a parsimonious model to predict physician consultation. RESULTS: 50.7% of the participants with headache reported at least one headache-specific physician consultation during lifetime. Of these, 53.6% had seen one, 26.1% two, and 20.3% more than two physicians because of their headaches. The odds of physician consultation increased with the number of headache days per month (HDM) [(reference HDM < 1) HDM 1-3 (OR = 2.29), HDM 4-14 (OR = 2.41), and HDM ≥15 (OR = 4.83)] and increasing Headache Impact Test score (HIT-6) [(reference "no or little impact") moderate impact (OR = 1.74), substantial impact (OR = 3.01), and severe impact (OR = 5.08)]. Middle-aged participants were more likely to have consulted than younger and older ones [(reference 14-34 years) 35-54 years (OR = 1.90), 55-74 years (OR = 1.96), ≥75 years (OR = 1.02)]. The odds of physician consultation among self-employed subjects were lower than among employed manual workers (OR = 0.48). The living environment (rural versus urban) did not have an influence on the consultation frequency. CONCLUSION: The results indicate that apart from burden-related factors (headache frequency; headache impact), health care utilization patterns are also influenced by patients' occupational status and age. Further research is needed to analyze whether the lower consultation rate means that the self-employed have a higher risk of chronification or that they have more effective self-management strategies regarding headache.

Author Correction: Small Neotropical primates promote the natural regeneration of anthropogenically disturbed areas.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

More Attacks and Analgesic Use in Old Age: Self-Reported Headache Across the Lifespan in a German Sample.

Background: Reliable population-based data on the prevalence and characteristics of primary headache across the lifespan are essential. However, robust data are lacking. Methods: We utilized questionnaire data from a random general population sample in Germany, that comprised 2,478 participants aged ≥14 years. A standardized questionnaire addressing headache and headache treatment was filled in during the face-to-face survey. Results: The 6-month prevalence of self-reported headache in the total sample amounted to 39.0% (known diagnosis of migraine 7.2%; tension-type headache 12.4%; another diagnosis or unknown diagnosis 23.4%). Age-specific prevalence rates were 37.9% (14-34 years), 44.6% (35-54 years), 38.5% (55-74 years), and 26.9% (≥75 years). Compared to age group 14-34, participants aged 35-54 were more (OR = 1.29, 95%-CI 1.05-1.60, p = 0.018) and those aged ≥75 were less (OR = 0.55, 95%-CI 0.40-0.76, p < 0.001) likely to have any headache. Of the participants with headache, 79.5% reported headache on <4 days per month, 15.6% on 4-14 days per month and 4.9% on >14 days per month. The frequency of headache did not differ significantly between age groups in men [ χ ( 3 ,   N   =   384 ) 2 = 1.45, p > 0.05], but in women [ χ ( 3 ,   N   =   651 ) 2 = 21.57, p < 0.001]: women aged ≥75 years were over-represented in the group reporting 4-14 headache days per month. The analgesic use (days per month) differed significantly between age groups among participants with headache on <4 days per month and on >14 days per month: 1.8 (14-34 years), 2.5 (35-54 years), 3.2 (55-74 years), and 3.4 (≥75 years), respectively 7.9 (14-34 years), 11.4 (35-54 years), 18.4 (55-74 years), and 22.8 (≥75 years). Conclusions: In general, the prevalence of headache decreases with age. However, older women suffer from more frequent attacks and older participants take analgesics on more days per month than younger participants. This might put them at risk of medication overuse which may lead to medication overuse headache. More research is needed to understand these specifics in headache frequency and treatment behavior in older people.

Small Neotropical primates promote the natural regeneration of anthropogenically disturbed areas.

Increasingly large proportions of tropical forests are anthropogenically disturbed. Where natural regeneration is possible at all, it requires the input of plant seeds through seed dispersal from the forest matrix. Zoochorous seed dispersal - the major seed dispersal mode for woody plants in tropical forests - is particularly important for natural regeneration. In this study, covering a period of more than 20 years, we show that small New World primates, the tamarins Saguinus mystax and Leontocebus nigrifrons, increase their use of an anthropogenically disturbed area over time and disperse seeds from primary forest tree species into this area. Through monitoring the fate of seeds and through parentage analyses of seedlings of the legume Parkia panurensis from the disturbed area and candidate parents from the primary forest matrix, we show that tamarin seed dispersal is effective and contributes to the natural regeneration of the disturbed area.

Familial NEDD4L variant in periventricular nodular heterotopia and in a fetus with hypokinesia and flexion contractures.

BACKGROUND: Mutations in the HECT domain of NEDD4L have recently been identified in a cohort of eight patients with a syndromic form of bilateral periventricular nodular heterotopia (PVNH) in association with neurodevelopmental delay, cleft palate, and toe syndactyly (PVNH7). METHODS: Case report based on NGS sequencing. RESULTS: Here, we describe a girl with a novel heterozygous NEDD4L missense variant, p.Tyr679His, and characteristic clinical findings, including bilateral periventricular nodular heterotopia, cleft palate and mild toe syndactyly. Molecular testing from peripheral blood identified the healthy father to carry the NEDD4L variant in mosaic state. Notably, a previous pregnancy of the couple had been terminated due to a complex fetal developmental disorder, including hypokinesia and flexion contractures. Upon review, this affected fetus was also shown to carry the familial NEDD4L variant. CONCLUSION: Our findings may suggest a broader spectrum of NEDD4L-associated phenotypes, including severe prenatal neurodevelopmental manifestations, which might represent yet another genetic form of fetal hypokinesia with flexion contractures.

The role of the surface smear microbiome in the development of defective smear on surface-ripened red-smear cheese.

The complex smear microbiota colonizing the surface of red-smear cheese fundamentally impacts the ripening process, appearance and shelf life of cheese. To decipher the prokaryotic composition of the cheese smear microbiome, the surface of a semi-hard surface ripened cheese was studied post-ripening by culture-based and culture-independent molecular approaches. The aim was to detect potential bacterial alterations in the composition of the cheese smear microbiota resulting from cheese storage in vacuum film-prepackaging, which is often accompanied by the development of a surface smear defect. Next-generation sequencing of amplified 16S rRNA gene fragments revealed an unexpected high diversity of a total of 132 different genera from the domains Bacteria and Archaea on the cheese surface. Beside typical smear organisms, our study revealed the presence of several microorganisms so far not associated with cheese, but related to milk, farm and cheese dairy environments. A 16S ribosomal RNA based analysis from total RNA identified the major metabolically active populations in the cheese surface smear as Actinobacteria of the genera Corynebacterium, Brevibacterium, Brachybacterium and Agrococcus. Comparison of data on a higher phylogenetic level revealed distinct differences in the composition of the cheese smear microbiome from the different samples. While the proportions of Proteobacteria and Bacteroidetes were increased in the smear of prepacked samples and in particular in defective smear, staphylococci showed an opposite trend and turned out to be strongly decreased in defective smear. In conclusion, next-generation sequencing of amplified 16S rRNA genes and 16S rRNA from total RNA extracts provided a much deeper insight into the bacterial composition of the cheese smear microbiota. The observed shifts in the microbial composition of samples from defect surface smear suggest that certain members of the Proteobacteria contribute to the observed negative organoleptic properties of the surface smear of cheese after prepacking in plastic foil.

Disruption of the plant-specific CFS1 gene impairs autophagosome turnover and triggers EDS1-dependent cell death.

Cell death, autophagy and endosomal sorting contribute to many physiological, developmental and immunological processes in plants. They are mechanistically interconnected and interdependent, but the molecular basis of their mutual regulation has only begun to emerge in plants. Here, we describe the identification and molecular characterization of CELL DEATH RELATED ENDOSOMAL FYVE/SYLF PROTEIN 1 (CFS1). The CFS1 protein interacts with the ENDOSOMAL SORTING COMPLEX REQUIRED FOR TRANSPORT I (ESCRT-I) component ELCH (ELC) and is localized at ESCRT-I-positive late endosomes likely through its PI3P and actin binding SH3YL1 Ysc84/Lsb4p Lsb3p plant FYVE (SYLF) domain. Mutant alleles of cfs1 exhibit auto-immune phenotypes including spontaneous lesions that show characteristics of hypersensitive response (HR). Autoimmunity in cfs1 is dependent on ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1)-mediated effector-triggered immunity (ETI) but independent from salicylic acid. Additionally, cfs1 mutants accumulate the autophagy markers ATG8 and NBR1 independently from EDS1. We hypothesize that CFS1 acts at the intersection of autophagosomes and endosomes and contributes to cellular homeostasis by mediating autophagosome turnover.

Progressive muscle relaxation reduces migraine frequency and normalizes amplitudes of contingent negative variation (CNV).

BACKGROUND: Central information processing, visible in evoked potentials like the contingent negative variation (CNV) is altered in migraine patients who exhibit higher CNV amplitudes and a reduced habituation. Both characteristics were shown to be normalized under different prophylactic migraine treatment options whereas Progressive Muscle Relaxation (PMR) has not yet been examined. We investigated the effect of PMR on clinical course and CNV in migraineurs in a quasi-randomized, controlled trial. METHODS: Thirty-five migraine patients and 46 healthy controls were examined. Sixteen migraineurs and 21 healthy participants conducted a 6-week PMR-training with CNV-measures before and after as well as three months after PMR-training completion. The remaining participants served as controls. The clinical course was analyzed with two-way analyses of variance (ANOVA) with repeated measures. Pre-treatment CNV differences between migraine patients and healthy controls were examined with t-tests for independent measures. The course of the CNV-parameters was examined with three-way ANOVAs with repeated measures. RESULTS: After PMR-training, migraine patients showed a significant reduction of migraine frequency. Preliminary to the PMR-training, migraine patients exhibited higher amplitudes in the early component of the CNV (iCNV) and the overall CNV (oCNV) than healthy controls, but no differences regarding habituation. After completion of the PMR-training, migraineurs showed a normalization of the iCNV amplitude, but neither of the oCNV nor of the habituation coefficient. CONCLUSIONS: The results confirm clinical efficacy of PMR for migraine prophylaxis. The pre-treatment measure confirms altered cortical information processing in migraine patients. Regarding the changes in the iCNV after PMR-training, central nervous mechanisms of the PMR-effect are supposed which may be mediated by the serotonin metabolism.

Disease duration of episodic migraine correlates with modified amplitudes and habituation of contingent negative variation.

Cortical habituation in episodic migraine patients without medication overuse headache (MOH), recorded by contingent negative variation (CNV), is often reduced compared with healthy controls. There is evidence that with longer duration of migraine disease (DOD) amplitudes and habituation of CNV become progressively abnormal. The aim of the study was to examine habituation characteristics of contingent negative variation in episodic migraine patients suffering from short- and long-lasting migraine compared to matched healthy controls. 32 migraine patients without aura and without MOH diagnosed according to the revised ICHD-II criteria and 16 age- and sex-matched healthy controls were included. According to DOD, the total sample of migraine patients was divided into two groups (group a: DOD <121 months, n = 17 subjects, group b: DOD >120 months, n = 15 subjects). Both migraine groups did not differ in the number of days of migraine and the duration of attacks. Overall CNV and initial CNV differed significantly between migraine patients and controls, whereas the former produced more negative amplitudes. In the migraine group lack of or deficient habituation occurred, whilst controls showed habituation. There were middle range correlations between the DOD and overall CNV, initial CNV, and y-intercept. Patients suffering from long-lasting migraine produced higher CNV amplitudes with a higher y-intercept. The results are interpreted as "maladaptive plasticity" with a risen intercept in long-lasting migraine.