Coming theses from other universities
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Postural Control Among Community Dwelling Older Adults
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:ltu:diva-110234
Background and aims
To address the increasing number of falls among the older population, this thesis sought to increase the understanding of the postural control among older adults. The specific aims was to explore: i) how muscular co-contractions affect postural control outcome for a novel surface perturbation task, and which sensorimotor variables that explain the level of co-contractions; ii) which sensorimotor variables and postural control strategies explain the ability to adapt to repeated surface perturbations; iii) the relationships of specific cognitive functions and parameters of postural control tasks; iv) the feasibility and potential effects of a tablet-based intervention for balance and cognitive functions.
Methods and results
In Study I and II, 45 adults (27 women) with a mean age of 75.5 years performed extensive sensorimotor testing and a repeated surface perturbation test while electromyography and kinematics were recorded. In Study I, a binominal regression analysis found that higher levels of agonist-antagonist co-contractions in response to a novel surface perturbation was associated with unsuccessful postural control. An OPLS – analysis found that higher levels of co-contractions were associated with female sex, poorer leg muscle strength, and slower processing speed. Co-contractions prior the perturbation did not explain task success, nor was it explained by sensorimotor variables.
In study II, an OPLS – Discriminative Analysis found that the inability to successfully adapt to three repeated surface perturbations was associated with higher age, poorer physical functioning, slower processing speed and poorer leg muscle strength. Postural control strategies that explained this were: less dorsiflexed ankles prior the third perturbation and more co-contractions of the lower legs in response to the third perturbation. Wilcoxon signed rank test found that the successful participants changed their starting position between trails by flexing their legs, whereas the unsuccessful did not.
In Study III, forty-six older adults (30 women) with a mean age of 74.5 years tested cognitive measures of global cognition, executive functions, and reaction time as well as discrete variables of walking, dual-task walking and postural sway in quiet stance. OPLS models found that longer step length and faster gait speed were related to faster processing speed and less intraindividual variability in a choice reaction test. Moreover, longer step length was also related to less fall-related concerns and less severe fall-related injuries, while faster gait speed was also related to female sex and poorer global cognition. Lower dual-task cost for gait speed was explained by faster processing speed and better inhibitory ability. Postural sway in quiet stance, step time or gait variability were not explained by cognitive functions.
In Study IV, twenty participants (10 women) with subjective cognitive decline participated in an eight-week tablet-based intervention. One group performed balance training three times a week and walked three times a week for at least 30 minutes. The second group additionally performed cognitive training three times a week. Recruitment via social media and senior organizations was considered successful. Adherence to the balance program was better in the group that only did the balance training and walking program. The balance training was well perceived but thought to be too easy. The cognitive training was well perceived but quite challenging, but adherence was high. No adverse events were reported. Assessments of fall-related concerns, cognitive functions and postural control indicated that the group that only performed balance training and walks got worse dual-task walking performance, whereas the group that also performed cognitive training improved their dual-task walking performance.
Conclusions
For a novel surface perturbation, high co-contraction reactions are associated with poorer postural control outcome, whereas physical capacity, cognitive functions and flexibility in postural strategies dictate if older adults can adapt to repeated postural challenges. Different cognitive processes explain discrete parameters of simple postural control tasks. To improve cognitive functions and postural control, a tablet-based intervention could be feasible, but should be flexible to accommodate different personal requirements, interactive to promote motivation and challenging enough to elicit positive adaptations.
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Electroanalytical Platforms Based on Textiles and Printed Circuit Boards for Point-of-Need Tests
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-354239
Point-of-need devices perform analytical tests that help inform decisions where they are needed, away from modern lab infrastructure, be it in-field or in resource-poor settings. They have many applications, including veterinary medicine, agriculture, food safety, environmental monitoring, and forensics. In medical diagnostics, such devices are called point-of-care tests, and they could help combat societal challenges such as the spread of epidemic diseases and providing adequate healthcare in developing countries. Point-of-care devices could also be wearable to non-invasively monitor body fluids such as sweat or urine from the patient. Ideal point-of-care devices conform with the REASSURED criteria, that they should be Real-time connected, Easy to collect samples, Affordable, Sensitive, Specific, User-friendly, Rapid, robust, Equipment-free, environmentally friendly, and Deliverable to the end user.
We have here developed Point-of-need devices based on textiles and Printed Circuit Boards (PCBs); both well-established technologies that could offer low-cost mass production using existing industrial resources. Specifically, we have made electrochemical biosensors based on gold-coated yarn in a rolling architecture, as well as combined with wicking Coolmax® yarn acting as microfluidic channels in wearable systems, enabling advanced textile-based diagnostic devices suitable for automation or machine-stitching into fabrics. We also showed biosensors based on gold-coated PCBs that can connect to portable potentiostats for electrochemical detection and have integrated heating for isothermal nucleic acid amplification.
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Endogenous and Exogenous Molecules Modulating Voltage-Gated Potassium Channels
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-208087
The superfamily of voltage-gated potassium (KV) channels is crucial for the normal function of several tissues and represents an attractive pharmacological target for treating disorders such as epilepsy and cardiac arrhythmias. However, any drug designed to target a KV channel must be capable of discriminating between different members within the superfamily, lest they plague the user with deleterious side effects. Such rational design requires structural and functional insight into how the selectivity of a molecule can be tailored to suit the intended target.
This thesis combines the use of electrophysiological and computational techniques to investigate the molecular basis for how the function of hKV7 and hERG channels can be modulated by different lipophilic compounds with known or suspected effects on ion channels. These include polyunsaturated fatty acids (PUFAs), cannabidiol (CBD), and synthetic cannabinoid receptor agonists (SCRAs).
Using the two-electrode voltage clamp technique on Xenopus oocytes, we find that both PUFAs and CBD modulate the function of hKV7 channels in subtype-specific manners. PUFAs facilitated the activation of hKV7 channels, except for hKV7.4 channels which were instead inhibited. Molecular dynamics simulations revealed that structural differences in the voltage-sensing domain of hKV7.4 conferred a unique, inhibitory PUFA interaction site absent in the other hKV7 subtypes. Once this site was neutralised by mutagenesis, PUFAs facilitated hKV7.4 activation. In the case of CBD, we observed three different responses: inhibition of channels with hKV7.1 subunits, potentiated voltage-sensitivity of channels with hKV7.2 or hKV7.3 subunits and enhanced maximum conductance of channels with hKV7.4 or hKV7.5 subunits. However, these responses were evoked from the same interaction site in the pore domain, indicating a more complex subtype-specific mechanism of action. Finally, using an automated patch-clamp system we screened 36 different SCRAs on the cardiac channels responsible for repolarisation: hERG and hKV7.1/KCNE1. We find 28 of the SCRAs to be inhibitors of hERG and 22 to be inhibitors of hKV7.1/KCNE1. Molecular dynamics simulations suggest the increased susceptibility of hERG to SCRA-mediated inhibition may be due to a unique central cavity site that is absent from the pore domain of hKV7.1/KCNE1.
In conclusion, structurally diverse lipophilic molecules of endogenous and exogenous origins can interact with KV channels and influence their function by enhancing or interfering with functional domains. In some instances, structural differences in the channel protein can explain the discrepancies in pharmacology. These findings have implications for both pharmacology (informing rational drug design) and toxicology (identifying targets through which adverse effects may occur).