Visual network activation in recovery from sensorimotor stroke

Recovery of finger movements after hemiparetic stroke has been shown to involve sensorimotor brain areas in perilesional and remote locations. Hand use, however, critically depends on visual guidance in such patients with stroke lesions in the middle cerebral artery territory. Using regional cerebral blood flow measurements, we wished to identify interrelated brain areas that are engaged in relation to manual activity in seven patients after their first hemiparetic brain infarction. During the blind-folded performance of sequential finger movements, the patients differed significantly from healthy controls (n = 7) by the recruitment of a predominantly contralesional network involving visual cortical areas, prefrontal cortex, thalamus, hippocampus, and cerebellum. Greater expression of this cortical-subcortical network correlated with a more severe sensorimotor deficit in the acute stage after stroke reflecting its role for post-stroke recovery. Patients also differed from controls on a lesion-related pattern expressed during rest. A third differentiating pattern involved the ipsilesional supplementary motor area and the contralesional premotor cortex. Our results suggest that post-stroke recovery form impaired sensorimotor integration utilizes crossmodal plasticity of a visual network.     

In Vitro ADME and Preclinical Pharmacokinetics of Ulotaront,a TAAR1/5-HT1A Receptor Agonist for the Treatment of Schizophrenia

Pharmaceutical Research - Ulotaront (SEP-363856) is a TAAR1 agonist with 5-HT1A agonist activity currently in clinical development for the treatment of schizophrenia. The objectives of the current...     

SARS-CoV-2-Seroprävalenz bei Kindern und Jugendlichen in Deutschland – ein Überblick

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - SARS-CoV-2-Antikörperstudien ergänzen und erweitern die Erkenntnisse aus der Meldestatistik laborbestätigter...     

Improved Stability of Proline-Derived Direct Thrombin Inhibitors through Hydroxyl to Heterocycle Replacement

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Protein–Protein Interactions: A Simple Strategy to Identify Binding Sites and Peptide Antagonists

Secondary structure motifs and small protein domains can act as building blocks that are isolated and investigated to gain insights into protein global structure but can also modulate interactions with external partners. Most progress has been made in this field using synthetic peptides. Fragmentation of folded proteins by proteolytic enzymes that act preferentially on exposed and less structured sites can help to isolate shorter polypeptides with preserved secondary and tertiary structures that mimic the original protein architecture. Such molecules can be used as probes for structural studies and as tools for in vitro assays to select active fragments useful as agonists or antagonists of the original protein or as scaffolds for the design of more potent and selective ligands. This simple but effective proteolytic methodology has been successfully applied to determine antagonists of protein–protein interactions, allowing the identification of inhibitors with high efficacy and specificity. Here, we present several studies including the complex between phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes and phospholipase 1, believed to play a relevant role in the insulin resistance mechanism in phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes‐overexpressing tissues, the self‐association of BCL10 caspase recruitment domain that mediates a protein oligomerization process responsible for NF‐κB activation and the self‐association of growth arrest and DNA damage‐inducible factor 45β, a major player of the endogenous NF‐κB‐mediated resistance to apoptosis.     

Lung, liver and bone cancer mortality in Mayak workers

Workers at the Mayak nuclear facility in the Russian Federation offer the only adequate human data for evaluating cancer risks from exposure to plutonium. Risks of mortality from cancers of the lung, liver and bone, the organs receiving the largest doses from plutonium, were evaluated in a cohort of 17,740 workers initially hired 1948-1972 using, for the first time, recently improved individual organ dose estimates. Excess relative risk (ERR) models were used to evaluate risks as functions of internal (plutonium) dose, external (primarily gamma) dose, gender, attained age and smoking. By December 31, 2003, 681 lung cancer deaths, 75 liver cancer deaths and 30 bone cancer deaths had occurred. Of these 786 deaths, 239 (30%) were attributed to plutonium exposure. Significant plutonium dose-response relationships (p < 0.001) were observed for all 3 endpoints, with lung and liver cancer risks reasonably described by linear functions. At attained age 60, the ERRs per Gy for lung cancer were 7.1 for males and 15 for females; the averaged-attained age ERRs for liver cancer were 2.6 and 29 for males and females, respectively; those for bone cancer were 0.76 and 3.4. This study is the first to present and compare dose-response analyses for cancers of all 3 organs. The unique Mayak cohort with its high exposures and well characterized doses has allowed quantification of the plutonium dose-response for lung, liver and bone cancer risks based on direct human data. These results will play an important role in plutonium risk assessment.     

Health outcomes measurement and organizational readiness support quality improvement: a systematic review

Background

Using outcome measures to advance healthcare continues to be of widespread interest. The goal is to summarize the results of studies which use outcome measures from clinical registries to implement and monitor QI initiatives. The second objective is to identify a) facilitators and/or barriers that contribute to the realization of QI efforts, and b) how outcomes are being used as a catalyst to change outcomes over time.

Methods

We searched the PubMed, EMBASE and Cochrane databases for relevant articles published between January 1995 and March 2017. We used a standardized data abstraction form. Studies were included when the following three criteria were fulfilled: 1) they relied on structural data collection, 2) when a structural and comprehensive QI intervention had been implemented and evaluated, and 3) impact on improving clinical and/or patient-reported outcomes was described. Data on QI strategies, QI initiatives and the impact on outcomes was extracted using standardized assessment tools.

Results

We included 21 articles, of which eight showed statistically significant improvements on outcomes using data from clinical registries. Out of these eight studies, the Chronic Care Model, IT application as feedback, benchmarking and the Collaborative Care Model were used as QI methods. Encouraging trends in realizing improved outcomes through QI initiatives were observed, ranging from improving teamwork, implementation of clinical guidelines, implementation of physician alerts and development of a decision support system. Facilitators for implementing QI initiatives included a high quality database, audits, frequent reporting and feedback, patient involvement, communication, standardization, engagement, and leadership.

Conclusion

This review suggests that outcomes collected in clinical registries are supportive to realize QI initiatives. Organizational readiness and an active approach are key in achieving improved outcomes.

     

A single measurement is inadequate to estimate enterolactone levels in danish postmenopausal women due to large intraindividual variation

Single measurements of enterolactone (ENL) used in epidemiologic studies are influenced by intraindividual variation. The objective of this controlled study was to investigate short-term intraindividual variations in serum and urine ENL. Based on these variations, the number of samples required to describe the basal ENL level was estimated. Healthy Danish postmenopausal women (n = 6) aged 54-67 y completed 3 study periods of 24 h within 2 mo. Blood samples were collected at 0, 4, 6, 8, 12, and 24 h and 24-h urine samples were collected. A low-lignan, standardized diet of 3 meals was served. ENL was measured by time-resolved fluoroimmunoassay. Intraindividual and interindividual variations were estimated using a mixed model with repeated measurements. Significant and systematic intraindividual within-day variations (CV) of 31% were observed in serum. Intraindividual day-to-day variations were 56% and overall intraindividual variation of samples collected at random times and on different days was estimated to be 64%. Describing this overall variation required 7 blood samples when estimated with a precision of 50% and 95% confidence. Day-to-day variations in 24-h urine samples were 49%. Large within-day and day-to-day variations suggest that a single measurement of ENL is inadequate to estimate the basal ENL level.