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Effects of Intensive Impairment-Oriented Arm Rehabilitation for Chronic Stroke Survivors: An Observational Cohort Study
Get PDFObjective: To assess the effects of a two-week course of intensive impairment-oriented arm rehabilitation for chronic stroke survivors on motor function.
Methods: An observational cohort study that enrolled chronic stroke survivors (≥6 months after stroke) with mild to severe arm paresis, who received a two-week course of impairment-oriented and technology-supported arm rehabilitation (1:1 participant–therapist setting), which was carried out daily (five days a week) for four hours. The outcome measures were as follows: the primary outcome was the arm motor function of the affected arm (mild paresis: BBT, NHPT; severe paresis: Fugl-Meyer arm motor score). The secondary outcomes were measures of finger strength, active ROM, spasticity, joint mobility/pain, somatosensation, emotional distress, quality of life, acceptability, and adverse events.
Results: One hundred chronic stroke survivors (≥6 months after stroke) with mild to severe arm paresis were recruited. The training was acceptable (drop-out rate 3%; 3/100). The clinical assessment indicated improved motor function (SMD 0.42, 95% CI 0.36–0.49; n = 97), reduced spasticity/resistance to passive movement, and slightly improved joint mobility/pain and somatosensation. The technology-based objective measures corroborated the improved active range of motion for arm and finger joints, reduced finger spasticity/resistance to passive movement, and the increased amount of use in daily life, but there was no effect on finger strength. The patient’s emotional well-being and quality of life were positively influenced. Adverse events were reported by the majority of participants (51%, 49/97) and were mild.
Conclusions: Structured intensive impairment-oriented and technology-supported arm rehabilitation can promote motor function among chronic stroke survivors with mild to severe arm paresis and is an acceptable and tolerable form of treatment when supervised and adjusted by therapists
Synthetic Approaches, Properties, and Applications of Acylals in Preparative and Medicinal Chemistry
Get PDFDiesters of geminal diols (R-CH(O-CO-R′)2, RR′C(OCOR″)2, etc. with R = H, aryl or alkyl) are termed acylals according to IUPAC recommendations (Rule P-65.6.3.6 Acylals) if the acids involved are carboxylic acids. Similar condensation products can be obtained from various other acidic structures as well, but these related “non-classical acylals”, as one might call them, differ in various aspects from classical acylals and will not be discussed in this article. Carboxylic acid diesters of geminal diols play a prominent role in organic chemistry, not only in their application as protective groups for aldehydes and ketones but also as precursors in the total synthesis of natural compounds and in a variety of organic reactions. What is more, acylals are useful as a key structural motif in clinically validated prodrug approaches. In this review, we summarise the syntheses and chemical properties of such classical acylals and show what potentially under-explored possibilities exist in the field of drug design, especially prodrugs, and classify this functional group in medicinal chemistry
Chemotaxis-dependent homing of innate lymphoid cells in the context of pregnancy
Get PDFPregnancy involves adaptations of the cellular composition in utero to establish a functioning fetal-maternal interface. Different subsets of leukocytes populate the endometrium and contribute to tolerance of the fetal allograft while protecting it from potentially threatening infections or rejection. ¬¬Innate lymphoid cells are recently discovered immune cells that, besides the gut, lung and skin, possess immunoregulatory functions in the female reproductive tract, especially during gestation. Although present at the fetal-maternal interface, the dynamics of ILC migration during pregnancy remains poorly investigated. The involvement of homing receptors in ILC migration to the uterus was the main subject of the present work.
First, the expression of homing receptors on ILCs from miscellaneous organs was assessed across the course of murine pregnancy in vivo by means of flow cytometry. Then, their migratory capacity towards pregnancy-relevant chemokines was investigated in vitro. The impact of pregnancy related hormones on the migration and homing of ILCs was then analysed in vitro via migration assays.
The results confirm altered proportions of ILCs in utero and the altered expression of homing receptors in ILCs in pregnancy. Different murine lymphoid organs showed augmented expression of chemokine receptors and decreased levels of homing integrin α4β7 in the first trimester, suggesting enhanced migration patterns of ILCs during early pregnancy. Subsequently, migration assays were used to demonstrate the role of different chemokine ligands in enhancing ILC migration.
Eventually, the alterations in homing receptor expression were correlated with female pregnancy hormones. Progesterone treatment caused similar effects on homing receptor expression in ILCs as observed during early gestation. These results represent the first study evaluating the effect of sex steroid hormones on ILC chemokine receptor distribution.
Taken together, our results indicate the involvement of pregnancy-relevant chemokines, including CCL4, CCL20 and CCL28, in the recruitment of ILCs to the uterus during pregnancy. The data highlight an endocrinological-immune crosstalk in the regulation of ILC homing to the female reproductive tract. Gestation alters chemokine receptor expression in order to regulate the access of immune cell subsets to the fetal-maternal interface. An adequate regulation is highly needed, as a lack or abundance of different subgroups could result in pregnancy complications, including fetal loss, pre-eclampsia or pre-term birth. Thus, the role of ILC chemotaxis to the pregnant uterus and its regulation are of interest in the understanding, prevention and treatment of the clinically relevant obstetric diseases
No Object–Location Memory Improvement through Focal Transcranial Direct Current Stimulation over the Right Temporoparietal Cortex
Get PDFRemembering objects and their associated location (object–location memory; OLM), is a fundamental cognitive function, mediated by cortical and subcortical brain regions. Previously, the combination of OLM training and transcranial direct current stimulation (tDCS) suggested beneficial effects, but the evidence remains heterogeneous. Here, we applied focal tDCS over the right temporoparietal cortex in 52 participants during a two-day OLM training, with anodal tDCS (2 mA, 20 min) or sham (40 s) on the first day. The focal stimulation did not enhance OLM performance on either training day (stimulation effect: −0.09, 95%CI: [−0.19; 0.02], p = 0.08). Higher electric field magnitudes in the target region were not associated with individual performance benefits. Participants with content-related learning strategies showed slightly superior performance compared to participants with position-related strategies. Additionally, training gains were associated with individual verbal learning skills. Consequently, the lack of behavioral benefits through focal tDCS might be due to the involvement of different cognitive processes and brain regions, reflected by participant’s learning strategies. Future studies should evaluate whether other brain regions or memory-relevant networks may be involved in the modulation of object–location associations, investigating other target regions, and further exploring individualized stimulation parameters
Metabolic cost of unloading pedalling in different groups of patients with pulmonary hypertension and volunteers
Get PDFRecently, the parameter internal work (IW) has been introduced as change in oxygen uptake (VO2) between resting and unloading workload in cardiopulmonary exercise testing (CPET). The proportional IW (PIW) was defined as IW divided by VO2 at peak exercise. A second option is to calculate the PIW based on the workload [PIW (Watt)] by considering the aerobic efficiency. The aim of our study was to investigate whether IW and PIW differ between patients with and without pulmonary hypertension and healthy controls. Our study population consisted of 580 patients and 354 healthy controls derived from the Study of Health in Pomerania. The PIW was slightly lower in patients (14.2%) than in healthy controls (14.9%; p = 0.030), but the PIW (Watt) was higher in patients (18.0%) than in the healthy controls (15.9%; p = 0.001). Such a difference was also observed, when considering only the submaximal workload up to the VAT (19.8% in patients and 15.1% in healthy controls; p < 0.001). Since the PIW (Watt) values were higher in patients with pulmonary hypertension, this marker may serve as a useful CPET parameter in clinical practice. In contrast to most of the currently used CPET parameters, the PIW does not require a maximal workload for the patient. Further studies are needed to validate the prognostic significance of the PIW
Retrospektive Analyse von Rezidivraten histographisch kontrollierter Exzisionen von Basalzellkarzinomen und Plattenepithelkarzinomen und die Analyse der psychosozialen Belastung durch die Tumorerkrankung dieser Kohorte von 2009-2011 über einen Beobachtungszeitraum von vier Jahren
Get PDFDurch weltweit steigende Inzidenzen des Nicht-melanozytären Hautkrebses und die hohen Rezidivraten dieser Malignome entsteht einerseits eine relevante Belastung der Gesundheitssysteme als auch eine individuelle Einschränkung der Lebensqualität der Patient*innen [4, 46, 47, 60].
Der Fokus der vorliegenden retrospektiven Studie liegt einerseits auf der Untersuchung signifikanter Risikofaktoren für die Rezidiventstehung bei NMSC und andererseits auf der Erhebung und Quantifizierung der psychosozialen Belastung der Patient*innen.
Eingeschlossen und eingewilligt in die Analyse haben 78 Patient*innen, die von 2009 bis 2011 ein Basalzellkarzinom oder Plattenepithelkarzinom in der Dermatologie der Universitätsmedizin in Greifswald diagnostiziert bekamen und diese histographisch kontrolliert exzidiert wurden.
Ein signifikanter Parameter der Entstehung eines Basalzellkarzinomrezidivs konnte in dieser Studie bestätigt werden. Die Immunsuppression ist als bedeutsamer Risikofaktor für die Entstehung von NMSC bekannt [37, 38, 74]. Daraus ergibt sich eine engmaschige Betreuung der Patient*innen, sowie Haut-Screenings und gegebenenfalls Behandlungen risikostratifiziert [95].
Für den zweiten Teil der vorgelegten Untersuchung wurde ein auf dem DLQI basierendes Assessment zur Quantifizierung der Quality of Life entwickelt und ausgewertet. Die Ergebnisse der Auswertungen bei BCC- und SCC-Patient*innen zeigen auf, dass es eine deutliche interindividuelle Spanne von gar keiner zu starker emotionaler Belastung durch diese Erkrankungen gibt. Es ist die Aufgabe der Behandler*innen beziehungsweise des behandelnden Personals herauszufiltern, welche Patient*innen stärker belastet sind und gegebenenfalls psychotherapeutische Hilfe benötigen [45, 46]. Außerdem konnte aufgezeigt werden, dass vor allem die Diagnosestellung belastend für die Patient*innen empfunden wird. Dieses Wissen sollte an die gesprächsführenden Ärzt*innen herangetragen werden und zu Schulungen zu Aufklärungsgesprächen bei schwerwiegenden Erkrankungen führen. Nur wenige Patient*innen hatten weiterhin Kenntnis vom psychoonkologischen Dienst der Universitätsklinik. Auch diesbezüglich besteht eine Aufklärungspflicht der Behandler*innen.
Die Untersuchungen sollten in nachfolgenden Studien mit größerer Fallzahl und längeren Beobachtungszeiträumen erfolgen, um einen erhöhten Grad an statistischer Signifikanz zu erreichen und deren Evidenz zu untermauern
Initiation of acute pancreatitis in mice is independent of fusion between lysosomes and zymogen granules
Get PDFThe co-localization of the lysosomal protease cathepsin B (CTSB) and the digestive zymogen trypsinogen is a prerequisite for the initiation of acute pancreatitis. However, the exact molecular mechanisms of co-localization are not fully understood. In this study, we investigated the role of lysosomes in the onset of acute pancreatitis by using two different experimental approaches. Using an acinar cell-specific genetic deletion of the ras-related protein Rab7, important for intracellular vesicle trafficking and fusion, we analyzed the subcellular distribution of lysosomal enzymes and the severity of pancreatitis in vivo and ex vivo. Lysosomal permeabilization was performed by the lysosomotropic agent Glycyl-L-phenylalanine 2-naphthylamide (GPN). Acinar cell-specific deletion of Rab7 increased endogenous CTSB activity and despite the lack of re-distribution of CTSB from lysosomes to the secretory vesicles, the activation of CTSB localized in the zymogen compartment still took place leading to trypsinogen activation and pancreatic injury. Disease severity was comparable to controls during the early phase but more severe at later time points. Similarly, GPN did not prevent CTSB activation inside the secretory compartment upon caerulein stimulation, while lysosomal CTSB shifted to the cytosol. Intracellular trypsinogen activation was maintained leading to acute pancreatitis similar to controls. Our results indicate that initiation of acute pancreatitis seems to be independent of the presence of lysosomes and that fusion of lysosomes and zymogen granules is dispensable for the disease onset. Intact lysosomes rather appear to have protective effects at later disease stages
A Targeted Approach for the Metabolome Analysis of E. coli Biofilms
Get PDFBiofilms of pathogenic bacteria are responsible for persistent infections in humans, therefore investigations of biofilm formation and treatment strategies are required. The gram‐negative enterobacterium Escherichia (E.) coli is the most common pathogen causing chronic or recurring urinary tract infections. Metabolomics approaches targeted the bacterium to investigate specific metabolic patterns of biofilms and regulatory influences on biofilm formation. In this study, we aimed to investigate the metabolome of biofilms formed by the multidrug‐resistant extended‐spectrum beta‐lactamase‐producing (ESBL) E. coli PBIO729. For this purpose, a protocol for fast sampling of the macrocolony biofilms and efficient extraction of metabolites was optimized. Validation of an LC‐MS/MS method confirmed its usability for the analysis of nucleotides and other phosphorylated metabolites. A GC‐MS approach was used to monitor nutrient uptake from the medium in addition to the analysis of amino acid content and metabolites of glycolysis and TCA cycle in E. coli biofilms
Two RNA Folds from One Sequence: A Ribozyme with Versatile Substrate Processing Abilities
Get PDFWe report the design of a single RNA sequence capable of adopting one of two ribozyme folds and catalyzing the cleavage and/or ligation of the respective substrates. The RNA is able to change its conformation in response to its environment, hence it is called chameleon ribozyme (CHR). Efficient RNA cleavage of two different substrates as well as RNA ligation by CHR is demonstrated in separate experiments and in a one pot reaction. Our study shows that sequence variants of the hairpin ribozyme intersect with the hammerhead ribozyme and that rather short RNA molecules can have comprehensive conformational flexibility, which is an important feature for the emergence of new functional folds in early evolution
Small Brains: Body Shape Constrains Tissue Allocation to the Central Nervous System in Ant‐Mimicking Spiders
Get PDFIn Batesian mimicry, mimetic traits are not always as convincing as predicted by theory—in fact, inaccurate mimicry with only a superficial model resemblance is common and taxonomically widespread. The “selection trade‐offs hypothesis” proposes a life‐history trade‐off between accurate mimetic traits and one or more vital biological functions. Here, using an accurate myrmecomorphic (ant‐mimicking) jumping spider species, Myrmarachne smaragdina , we investigate how myrmecomorphic modifications to the body shape impact the internal anatomy in a way that could be functionally limiting. Specifically, via x‐ray micro‐computed tomography (microCT), we quantify how the spider's constricted prosoma, which emulates the head and thorax of ants, impacts the size of the central nervous system (CNS) and the venom glands. Although, relative to their whole‐body mass, we found no significant difference in venom gland volume, the CNS of the ant‐mimicking jumping spider was significantly smaller when compared with a relatively closely related non‐mimic jumping spider, indicating that some trade‐off between mimic accuracy and size of neural anatomy, as articulated by the “selection trade‐offs hypothesis,” is a possibility. Our explorative evidence enables and encourages broader investigation of how variable mimic accuracy impacts the neuroanatomy in ant mimics as a direct test of the “selection trade‐offs hypothesis.