Identifizierung und Charakterisierung von CREM-Spleißvarianten im murinen und humanen Herzen

In der Progression der Herzinsuffizienz spielen die beta-adrenerge Stimulation und die folgende Aktivierung des cAMP-abhängigen Signaltransduktionsweges eine wichtige Rolle. Transkriptionsfaktoren wie CREM (cAMP Responsive Element Modulator) regulieren die Transkription ihrer Zielgene in Abhängigkeit vom cAMP-Level. Das CREM-Gen besitzt 14 Exons und kann durch sechs intronische Promotoren eine Vielzahl von Isoformen hervorbringen. In dieser Arbeit wurde das kardiale Expressionsmuster der CREM-Isoformen in humanen und murinen Herzen detailliert charakterisiert. Eine repressorische Funktion der Spleißvarianten auf die Transkription liegt nahe. Unter beta-adrenerger Stimulation konnte eine charakteristische Kinetik der untersuchten Spleißvarianten im murinen Herzen beobachtet werden. Ein Vergleich der Expression von CREM-Spleißvarianten in Herzen von Patienten mit dilatativer Kardiomyopathie mit nicht insuffizienten Spenderherzen zeigte eine signifikante Induktion des Transkripts B-H-Ib. Die erhobenen Daten belegen, dass multiple CREM-Isoformen zur transkriptionellen Regulation der beta-adrenergen Stimulation am Herzen beitragen. Somit kann CREM vor allem durch die inhibitorische Modulation der Genexpression an der Progression der Herzinsuffizienz beteiligt sein

Factors associated with health insurance status in an Asian American population in New York City : analysis of a community-based survey

Background Immigrants comprise approximately 13% of the US population and 33% lack health coverage. Asian Americans are the fastest growing immigrant group; many lack a usual source of care. This study examines factors associated with health insurance among Asian American immigrants living in New York City. Methods Community needs assessments were conducted among Asian American subgroups in New York City from 2013- 2015; analysis was completed in 2017 and 2018. Descriptive statistics examined factors associated with health insurance status while stratifying by Asian ethnic subgroup; multivariable logistic regression models further assessed these associations (P<0.05 significance level). Results Approximately 19% of the study population (n=1,399) was uninsured. Logistic regression models adjusted for all factors. Among East Asians, insurance status was associated with female sex (OR=2.8, p=0.005), excellent/very good health status (OR=3.5, p=0.014), and seeing a private doctor when sick or injured (OR=3.2, p=0.033). Among South Asians, insurance status was associated with high school/some college and college education (OR=2.6 and 2.9, respectively, p=0.039 and p=0.021), having a routine health check in the past year (OR=6.4, p20 years (OR=3.7, p=0.009), having a routine health check in the past year (OR=5.6, p=0.025), and seeing a private doctor when sick or injured (OR=2.6, p=0.018). Conclusions Health insurance status was associated with differing factors among each subgroup. Findings may inform strategies to address challenges and barriers of healthcare access to immigrants, making healthcare more accessible to this underserved population

Modulation of Reaction Times and Sense of Agency via Subliminal Priming in Functional Movement Disorders.

Background: In functional movement disorders, explicit movements are impaired, while implicit movements are preserved. Furthermore, there is evidence that the sense of agency is abnormal. Aim: We aimed to investigate how motor responses and sense of agency were affected by subliminal or supraliminal cues in people with functional movement disorders. Methods: Twenty-three people with a functional movement disorder and 26 healthy controls took part in a subliminal and supraliminal priming experiment which investigated reaction times, choice and sense of agency. Participants pressed a left or right arrow key in response to an imperative left or right pointing arrow. Either key could be pressed in response to bidirectional arrows. The imperative arrow was preceded by a small left or right pointing prime arrow, that was non-predictive (50% correct) and was presented in either subliminal or supraliminal conditions. The participant's response caused the appearance of a colored circle and they rated the degree of control they felt over its appearance (sense of agency). The circle's color depended on whether their response was congruent or incongruent with the prime arrow direction. After exclusion, 19 participants remained in each group. Results: Prime-compatible responses led to faster reaction times in both the subliminal and supraliminal condition. Subliminal prime-compatible responses were chosen more frequently in the free choice condition. The sense of agency did not depend on prime-response congruency. There were no significant differences in any of these measures between the two groups. Conclusion: With non-predictive cues, reaction times, choices, and the sense of agency remain normal in people with functional movement disorders, for both subliminal and supraliminal primes. The findings suggest that it is not so much conscious awareness of the movement, but rather conscious motor preparation that is detrimental to motor function in functional movement disorders

A Case of Brain Abscess Caused by Propionibacterium acnes 13 Months after Neurosurgery and Confirmed by 16S rRNA Gene Sequencing

Propionibacterium acnes is a gram-positive anaerobic bacillus and a normal inhabitant of the skin. Although it is often considered a contaminant of blood cultures, it can occasionally cause serious infections, including postoperative central nervous system infections. Here, we report the case of a 70-yr-old man who developed a large cerebral abscess caused by P. acnes 13 months after neurosurgery. Immediate gram staining of the pus from his brain revealed the presence of gram-positive coccobacilli. However, colony growth was observed only after 5 days of culture. Therefore, we performed 16S rRNA gene sequencing of the pus specimen. The isolate was identified as P. acnes. The colonies developed 9 days after the initial culture. The API Rapid ID 32A test (bioMérieux, France) was performed using a colony, but an unacceptable profile was obtained. Then, the pus was transferred into the enrichment broths of the BACTEC FX (Becton Dickinson, USA) and BacT/Alert 3D (bioMérieux, Organon Teknika, USA) systems, but only the BACTEC FX system could detect growth after 5 days. We performed 16S rRNA gene sequencing and API Rapid 32A profiling with a colony recovered from Brucella agar, which was inoculated with the microbial growth in the enrichment broth from the BACTEC FX system. The organism was identified as P. acnes by both methods. This case suggests that 16S rRNA gene sequencing may be a useful alternative for identifying slowly growing P. acnes from specimens that do not show growth after 5 days of culture

Neurobiology of functional (psychogenic) movement disorders.

PURPOSE OF REVIEW: This review explores recent developments in understanding the neurobiological mechanism of functional (psychogenic) movement disorders (FMDs). This is particularly relevant given the resurgence of academic and clinical interest in patients with functional neurological symptoms and the clear shift in diagnostic and treatment approaches away from a pure psychological model of functional symptoms. RECENT FINDINGS: Recent research findings implicate three key processes in the neurobiology of FMD (and by extension other functional neurological symptoms): abnormal attentional focus, abnormal beliefs and expectations, and abnormalities in sense of agency. These three processes have been combined in recent neurobiological models of FMD in which abnormal predictions related to movement are triggered by self-focused attention, and the resulting movement is generated without the normal sense of agency that accompanies voluntary movement. SUMMARY: New understanding of the neurobiology of FMD forms an important part of reappraising the way that patients with FMD (and other functional disorders) are characterized and treated. It also provides a testable framework for further exploring the pathophysiology of these common causes of ill health

Pregnancy in multiple system atrophy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Multiple system atrophy is a late, adult-onset α-synucleinopathy with no data on the effect of pregnancy on the disease course. Early stage multiple system atrophy can be difficult to distinguish from Parkinson's disease.</p> <p>Case presentation</p> <p>We describe the case of an Irish woman with parkinsonism starting at age 31, initially diagnosed as having dopa-responsive, idiopathic Parkinson's disease, who successfully delivered a full-term child at age 35. Her pregnancy was complicated by severe orthostatic hypotension and motor fluctuations. Two years post-partum, she underwent bilateral subthalamic nuclei deep brain stimulation for intractable motor fluctuations and disabling dyskinesia. After this treatment course she experienced deterioration of motor symptoms and death eight years after disease onset. Post-mortem neuropathological examination revealed striatonigral degeneration and α-synuclein-positive glial cytoplasmic inclusions in brain stem nuclei, basal ganglia and white matter tracts, consistent with a neuropathological diagnosis of multiple system atrophy.</p> <p>Conclusions</p> <p>Multiple system atrophy can affect women of child-bearing age and pregnancy may be associated with marked disease progression.</p

Assessing changes in the food retail environment during the COVID-19 pandemic: opportunities, challenges, and lessons learned

Background COVID-19 mitigation strategies have had an untold effect on food retail stores and restaurants. Early evidence from New York City (NYC) indicated that these strategies, among decreased travel from China and increased fears of viral transmission and xenophobia, were leading to mass closures of businesses in Manhattan’s Chinatown. The constantly evolving COVID −19 crisis has caused research design and methodology to fundamentally shift, requiring adaptable strategies to address emerging and existing public health problems such as food security that may result from closures of food outlets. Objective We describe innovative approaches used to evaluate changes to the food retail environment amidst the constraints of the pandemic in an urban center heavily burdened by COVID-19. Included are challenges faced, lessons learned and future opportunities. Methods First, we identified six diverse neighborhoods in NYC: two lower-resourced, two higher-resourced, and two Chinese ethnic enclaves. We then developed a census of food outlets in these six neighborhoods using state and local licensing databases. To ascertain the status (open vs. closed) of outlets pre-pandemic, we employed a manual web-scraping technique. We used a similar method to determine the status of outlets during the pandemic. Two independent online sources were required to confirm the status of outlets. If two sources could not confirm the status, we conducted phone call checks and/or in-person visits. Results The final baseline database included 2585 food outlets across six neighborhoods. Ascertaining the status of food outlets was more difficult in lower-resourced neighborhoods and Chinese ethnic enclaves compared to higher-resourced areas. Higher-resourced neighborhoods required fewer phone call and in-person checks for both restaurants and food retailers than other neighborhoods. Conclusions Our multi-step data collection approach maximized safety and efficiency while minimizing cost and resources. Challenges in remote data collection varied by neighborhood and may reflect the different resources or social capital of the communities; understanding neighborhood-specific constraints prior to data collection may streamline the process

Metacognition of intentions in mindfulness and hypnosis

In a famous series of experiments, Libet investigated the subjective timing of awareness of an intention to move, a task that can be considered a metacognitive judgement. The ability to strategically produce inaccurate metacognitions about intentions has been postulated to be central to the changes in judgements of agency common to all hypnotic responding. Therefore, differences in hypnotisability may be reflected in Libet’s measure. Specifically, the ability to sustain inaccurate judgements of agency displayed by highly hypnotisable people may result from their having coarser higher order representations of intentions. They therefore should report a delayed time of intention relative to less hypnotisable individuals. Conversely, mindfulness practice aims at accurate metacognition, including of intentions, and may lead to the development of finer grained higher order representations of intending. Thus, the long-term practice of mindfulness may produce an earlier judgement of the time of an intention. We tested these groups using Libet’s task, and found that, consistent with predictions, highly hypnotisable people reported a later time of intention than less hypnotisable people and meditators an earlier time than non-meditators. In a further two studies we replicated the finding that hypnotisable people report later awareness of a motor intention and additionally found a negative relationship between trait mindfulness and this measure. Based on these findings, we argue that hypnotic response and meditation involve opposite processes

Illusory temporal binding in meditators

We investigate conditions in which more accurate metacognition may lead to greater susceptibility to illusion; and thus conditions under which mindfulness meditation may lead to less accurate perceptions. Specifically, greater awareness of intentions may lead to an illusory compression of time between a voluntary action and its outcome (“intentional binding”). Here we report that experienced Buddhist mindfulness meditators rather than non-meditators display a greater illusory shift of the timing of an outcome towards an intentional action. Mindfulness meditation involves awareness of causal connections between different mental states, including intentions. We argue that this supports improvements in metacognition targeted at motor intentions. Changes in metacognitive ability may result in an earlier and less veridical experience of the timing of action outcomes either through increased access to sensorimotor pre-representations of an action outcome or by affording greater precision to action timing judgements. Furthermore, as intentional binding is an implicit measure of the sense of agency, these results also provide evidence that mindfulness meditators experience a stronger sense of agency