Exercise as Disease-Modifying Strategy for Parkinson's: a Multidimensional Assessment of Acute and Long-Term Interventions

Parkinson's Disease (PD) is a complex and variable neurodegenerative condition. Due to its progressive nature and lack of effective treatments, a range of motor and non-motor symptoms develop and, usually, lead to disability and disengagement with active lifestyles. Exercise interventions have the potential of improving and sustaining physical and cognitive function in PD, as well as stimulating functional and structural neuroplasticity. Published research suggests that multi-modal (MM) exercise, that also includes cognitive tasks, may be more beneficial than single modalities in improving physical and/or cognitive function. However, there have been contrasting results between studies, owing to differences in study design (mode, timing, amount, and intensity of the exercise) and analytical methods used to measure biomarkers, which makes it difficult to generate conclusions and definitive exercise guidelines for people with PD (PwP). As a result of this, the overall objectives of this thesis were to propose acute and long-term interventions that are beneficial for PwP and can be implemented in real-world settings (at home or in the community), investigate associated functional and cognitive outcomes concurrently, and assess potential mechanisms underlying the neuroprotective effects of exercise interventions (MM, aerobic and combined exercise with cognitive tasks) completed in real-world or clinical environments. The first study (presented in Chapter 3) evaluates neurotrophins levels (i.e., BDNF and pro-BDNF) as candidate biomarkers for PwP in several sample types (plasma, serum, and saliva) with the aim of improving current inconsistent methodologies that compromise the reliability and validity of these measurements. Optimisation trials of ELISA assays were completed and revealed that the use of an appropriate combination of reagent diluent for each sample type and analyte is key to improve assay performance and measurement accuracy. The samples collected for the studies presented in Chapters 4 and 6 were subsequently analysed following the methodological steps reported in this study. Future work should include these methodological considerations and previous studies not reporting these details must be interpreted with caution. The second study (Chapter 4) presents the long-term implementation of a weekly community-based MM exercise programme for PwP and shows that exercise attendees improve and maintain function for up to 1, 2 or 3 years. Compared to non-active PwP, PD exercisers improve their mobility, lower extremity strength, cognition and BDNF levels, slowing down PD progression. Subsequently, focus groups were conducted in the studies presented in chapters 5 and 7 to gain in- depth understanding of participants' views about the MM exercise class and its change towards an online delivery due to the coronavirus 2019 (COVID-19) pandemic. Participant's discussions about the feasibility, practicality, and perceptions of the online class for PD, were gathered to develop guidelines for the online delivery of exercise for PwP. Finally, using an experimental laboratory setting, chapter 6 further explores the neuroprotective effects of acute bouts of aerobic exercise (alone or combined with cognitively challenging tasks) on cognitive function. This pilot study provides preliminary evidence of the beneficial effects that, both, a second bout of cycling 24h after the first session and cycling combined with cognitive tasks have on cognitive function. Taken together, both the optimisation and lab-based experimental studies provide directions for future research, such as methodological steps to ensure accurate BDNF and pro-BDNF measurements and exercise interventions that are suggested to elicit cognitive benefits. Furthermore, this thesis provides evidence that a community-based MM exercise programme is able to improve and maintain physical and cognitive functions in PwP. This intervention offered an evidence-based exercise class that had been running for over 4 years and, following COVID-19 pandemic, transitioned from the community towards an online-based setting where it has been successfully running for the last 2 years and is ongoing. Accordingly, this thesis also provides novel insights into the online delivery of MM exercise for PwP and presents guidelines for an appropriate setting-up and delivery of online exercise programmes for health-care professionals and researchers working with PwP

Advances in flow cytometry in basic and applied equine andrology

El objetivo de esta revisión es presentar las sondas actuales disponibles que evalúan diferentes compartimentos y funciones de los espermatozoides de los sementales, incluidos ensayos para investigar la funcionalidad de las membranas, el núcleo y las mitocondrias, y estudiar la señalización celular en esta célula en particular. También se presentarán los nuevos protocolos multiparamétricos para la evaluación de espermatozoides de sementales, recientemente desarrollados en el laboratorio de los autores. También se discutirá la aplicabilidad clínica potencial de las pruebas de diagnóstico basadas en citometría de flujo.The aim of this review is to present the current probes available that assess different compartments and functions of stallion spermatozoa, including assays to investigate the functionality of the membranes, nucleus and mitochondria, and to study cell signaling in this particular cell. New multi-parametric protocols for the assessment of stallion sperm, recently developed in the laboratory of the authors, will also be presented. The potential clinical applicability of diagnostic tests based on flow cytometry will also be discussed.Trabajo financiado por: Ministerio de Economía y Competitividad y Fondos FEDER. Ayuda AGL2013-43211-R Junta de Extremadura y Fondos FEDER. Ayuda GR 15029 Ministerio de Educación, Cultura y Deporte. Beca FPU13/03991, para Patricia Martín Muñoz Ministerio de Economía y Competitividad. Beca Juan de la Cierva” IJCI-2014-21671, Cristina Ortega FerrusolapeerReviewe

Evaluation of Phase IV Cardiac Rehabilitation Exercise Training in Stroke Survivors

EVALUATION OF PHASE IV CARDIAC REHABILITATION EXERCISE TRAINING IN STROKE SURVIVORS S. Meadows and A. Ferrusola-Pastrana School of Sport and Exercise Sciences, University of Kent Abstract Aims To evaluate health and functional fitness parameters of stroke survivors participating in a Phase IV style cardiac rehabilitation circuit class. Introduction: Stroke is a leading cause of mortality and disability worldwide and the economic costs of treatment and post-stroke care are substantial. Therefore, interventions to help with risk factor management and aid stroke recovery are needed. Exercise training (cardiovascular & strength) offers a potential means to alleviate the burden associated with long-term disability and improve stroke survivor quality of life (QoL). Methods 25 stroke survivors (male = 11; female = 14; mean age 59.5 ± 14.3years) with at least 3-months engagement in a weekly Phase IV-style circuit exercise class completed anthropometric (body mass index [BMI] and waist circumference), health (resting blood pressure), and functional capacity measurements (6-minute shuttle walking distance [6MWD], timed up and go [TUG] and bilateral grip strength [GS]). Results Mean BMI did not significantly change (28.77 ± 4.89kg/m2 to 29.12 ± 5.32kg/m2). Regional weight distribution measured by waist circumference remained similar. Resting blood pressure decreased significantly (SBP p<0.001; DBP p<0.03) with mean SBP decreasing by 7.77% to achieve clinical significance to a normotensive value (131 ± 14mmHg). 6MWD improved (p<0.001) from a mean of 351 ± 100m to 432 ± 113m (19.80% improvement). TUG performance was 12.19% quicker (p<0.006), as was left (p<0.03) & right (p<0.02) GS (8.85% and 32.04%, respectively). Conclusion Circuit-based exercise training offers considerable health and functional capacity benefits to stroke survivors potentially helping to promote recovery, QoL and reduce the disability burden

El subsòl de la ciutat: antics subterranis de Vilanova i la Geltrú

A la ciutat de Vilanova i la Geltrú existeixen una sèrie d’antigues construccions subterrànies, de les quals no existeix molta informació. Sobre aquestes construccions del subsòl de la ciutat hi ha diferents hipòtesis, entre les quals es destaquen els refugis de conflictes armats, els túnels d’escapada, les fresqueres i concretament els refugis de la guerra civil espanyola. També es diu que entre aquests túnels existeix una connexió que recorre gran part del subsòl de la ciutat. El treball s’elabora a partir de la documentació obtinguda per historiadors de la ciutat, que han mostrat un gran interès per aquest tema tan nombrat i tan poc conegut a la vegada. La informació existent sobre aquest tema és dispersa i els plànols existents no han estat mai posats en un context comú; no existeix un plànol dels soterranis situats al subsòl de la ciutat. En aquest treball es recopila la informació existent i es realitza un nou plànol del subsòl de la ciutat que conté tots els soterranis de Vilanova i l a Geltrú, que posa en valor aquestes construccions subterrànies. Amb aquest plànol es pretén posar una capa més sobre la ciutat, fins ara oblidada. Per reivindicar aquest patrimoni ocult, a partir del plànol que he elaborat del subsòl de Vilanova i la Geltrú, es relaciona la part sota rasant de la ciutat amb la superfície, per tal de crear uns vincles entre el sobre i el sota de la ciutat. Amb aquests vincles es detecten diferents punts de la ciutat, a partir d’aquests, es proposa crear uns recorreguts per la ciutat, que permetin descobrir el patrimoni del subsòl i conèixer la història de Vilanova i la Geltrú. A més a més es proposa la rehabilitació d’algunes d’aquestes construccions per tal de recuperar patrimoni

The therapeutic effects of multimodal exercise for people with Parkinson's: A longitudinal community-based study

Abstract Introduction Individuals with Parkinson’s Disease (PD) can develop a range of motor and non-motor symptoms due to its progressive nature and lack of effective treatments. Exercise interventions, such as multimodal (MM) programmes, may improve and sustain physical or cognitive function in PD. However, studies usually evaluate physical performance, cognition, and neuroprotective biomarkers separately and over short observation periods. Methods Part one evaluates the effects of a weekly community-based MM exercise class (60 min) on physical function in people with PD (PwP). Exercise participants (MM-EX; age 65 ± 9 years; Hoehn and Yahr (H&Y) scale ≤ IV) completed a battery of functional assessments every 4 months for one (n = 27), two (n = 20) and three years (n = 15). In part two, cognition and brain-derived neurotrophic factor (BDNF) levels were assessed over 6-to-8 months and compared to aged-matched non-active PwP (na-PD, n = 16; age 68 ± 7 years; H&Y scale ≤ III) and healthy older adults (HOA, n = 18; age 61 ± 6 years). Results MM-EX significantly improved walking capacity (5% improvement after 8 months), functional mobility (11% after 4 months), lower extremity strength (15% after 4 months) and bilateral grip strength (9% after 28 months), overall, maintaining physical function across 3 years. Group comparisons showed that only MM-EX significantly improved their mobility, lower extremity strength, cognition and BDNF levels. Conclusion Weekly attendance to a community-based MM exercise group session can improve and maintain physical and cognitive function in PD, with the potential to promote neuroprotection

Autophagy and Apoptosis Have a Role in the Survival or Death of Stallion Spermatozoa during Conservation in Refrigeration

Apoptosis has been recognized as a cause of sperm death during cryopreservation and a cause of infertility in humans, however there is no data on its role in sperm death during conservation in refrigeration; autophagy has not been described to date in mature sperm. We investigated the role of apoptosis and autophagy during cooled storage of stallion spermatozoa. Samples from seven stallions were split; half of the ejaculate was processed by single layer centrifugation, while the other half was extended unprocessed, and stored at 5°C for five days. During the time of storage, sperm motility (CASA, daily) and membrane integrity (flow cytometry, daily) were evaluated. Apoptosis was evaluated on days 1, 3 and 5 (active caspase 3, increase in membrane permeability, phosphatidylserine translocation and mitochondrial membrane potential) using flow cytometry. Furthermore, LC3B processing was investigated by western blotting at the beginning and at the end of the period of storage. The decrease in sperm quality over the period of storage was to a large extent due to apoptosis; single layer centrifugation selected non-apoptotic spermatozoa, but there were no differences in sperm motility between selected and unselected sperm. A high percentage of spermatozoa showed active caspase 3 upon ejaculation, and during the period of storage there was an increase of apoptotic spermatozoa but no changes in the percentage of live sperm, revealed by the SYBR-14/PI assay, were observed. LC3B was differentially processed in sperm after single layer centrifugation compared with native sperm. In processed sperm more LC3B-II was present than in non-processed samples; furthermore, in non-processed sperm there was an increase in LC3B-II after five days of cooled storage. These results indicate that apoptosis plays a major role in the sperm death during storage in refrigeration and that autophagy plays a role in the survival of spermatozoa representing a new pro-survival mechanism in spermatozoa not previously described

Dataset of endometrial blood flow from pregnant and non-pregnant mares on day 7 and 8 post-ovulation

This article provides the dataset for the use of power Doppler ultrasound to assess the equine uterus from the recent research article titled “Power Doppler can detect the presence of 7-8 days conceptuses prior to flushing in an equine embryo transfer program”(1). The vascularization of the endometrium was objectively assessed in mares by quantification of pixels in bitmap format (BMP) using computer assisted analysis of images. Fifty-two mares were examined on days 7 (26 mares) and 8 (26 mares) post-ovulation prior to performing flushing procedures for embryo recovery. Receiver operating characteristic (ROC) curves and Youden's J statistics were used to evaluate the value of the suggested variable in terms of its diagnostic value for identification of early pregnancy and to establish cut-off values allowing differentiation between pregnant and non-pregnant mares on days 7 and 8 post-ovulation

Group-based exercise for Parkinson’s: a qualitative study of participants and partners’ perceptions of an exercise class delivered through a community-university collaboration

Background Community-based exercise programmes (CBEPs) offer a practical and viable approach to providing people with Parkinson's disease (PwP) the opportunity to exercise as an ancillary therapeutic benefit to pharmacological management. This study explores the perceptions of exercising participants (PwP) and non-participating partners involved in an exercise class delivered through a community-university partnership. Methods Two separate focus group discussions were conducted: one with class participants (PwP: n = 7, H&Y scale I to III), and the other with non-participating partners of PwP (n = 4). Results Thematic analysis of the data identified that a range of physical, psychological and social factors were perceived to influence engagement: (1) actively taking control, (2) exercise is medicine for the mind and body, and (3) a community working together to promote exercise for parkinson's. Participants and partners felt that the support from the group, including the instructors and student volunteers, empowered and supported PwP to proactively self-manage their health, enjoy exercise in an inclusive group setting, and develop strong social connections with others in the local Parkinson's community. Support to exercise from healthcare professionals was identified as both an enabler and barrier to participation. Conclusions This study underscores the significance of a community-university partnership as a complementary therapeutic approach for PwP. It also provides critical reflections on its sustainability, including implications for how exercise is considered as medicine for PwP. Additionally, it offers practical recommendations to galvanise community participation and provide inclusive and viable exercise opportunities for PwP

Group-based exercise for Parkinson’s: a qualitative study of participants and partners’ perceptions of an exercise class delivered through a community-university collaboration

Background Community-based exercise programmes (CBEPs) offer a practical and viable approach to providing people with Parkinson's disease (PwP) the opportunity to exercise as an ancillary therapeutic benefit to pharmacological management. This study explores the perceptions of exercising participants (PwP) and non-participating partners involved in an exercise class delivered through a community-university partnership. Methods Two separate focus group discussions were conducted: one with class participants (PwP: n = 7, H&Y scale I to III), and the other with non-participating partners of PwP (n = 4). Results Thematic analysis of the data identified that a range of physical, psychological and social factors were perceived to influence engagement: (1) actively taking control, (2) exercise is medicine for the mind and body, and (3) a community working together to promote exercise for parkinson's. Participants and partners felt that the support from the group, including the instructors and student volunteers, empowered and supported PwP to proactively self-manage their health, enjoy exercise in an inclusive group setting, and develop strong social connections with others in the local Parkinson's community. Support to exercise from healthcare professionals was identified as both an enabler and barrier to participation. Conclusions This study underscores the significance of a community-university partnership as a complementary therapeutic approach for PwP. It also provides critical reflections on its sustainability, including implications for how exercise is considered as medicine for PwP. Additionally, it offers practical recommendations to galvanise community participation and provide inclusive and viable exercise opportunities for PwP

Power Doppler can detect the presence of 7–8 day conceptuses prior to flushing in an equine embryo transfer program

In order to determine whether differences in uterine blood flow between pregnant and non-pregnant mares can be used to predict the presence of the equine embryo prior to flushing in an embryo transfer program, power Doppler ultrasonography was used on a total of 52 mares on days 7 or 8 post-ovulation. Computer analysis of Doppler images was subsequently performed using ImageJ v1.48 software. Vascular perfusion of the endometrium was analyzed using spot meter techniques, measuring mean pixel intensity and area of blood flow. Mares with positive flushings presented a higher uterine blood flow area (one embryo: 54.01 ± 2.27 mm2 or two embryos: 61.01 ± 6.73 mm2) prior to embryo recovery compared to barren mares (21.77 ± 2.22 mm2) (p ≤ 0.05). However, significant differences in vascular perfusion were not detected between single or twin pregnancies. Blood flow area appears to be a good predictor for differentiation between pregnant and non-pregnant mares with an AUC: 0.869; p ≤ 0.001 and an optimal cut-off value of 37.21 mm2. Both the mare's age and day of embryo recovery caused effects on uterine vascular perfusion. According to Youden's J statistics the uterine blood flow area of young pregnant mares was greater than 25.4 mm2 on day 7 (with a sensitivity of 75% and a specificity of 87.5%) and greater than 21.02 mm2 on day 8 post-ovulation (with a sensitivity of 93.8% and a specificity of 100%). The uterine blood flow area in adult pregnant mares was greater than 41.4 mm2 on day 7 (with a sensitivity of 80% and a specificity of 85.5%) and greater than 35.55 mm2 on day 8 after ovulation (with a sensitivity of 97.2% and a specificity of 85.7%). Evaluation on day 8 is therefore considered to be more reliable. Older and middle aged pregnant mares (5–18 years old) had increased uterine vascularization compared to young pregnant mares (2–5 years old) (p ≤ 0.001). Conversely, older barren mares showed higher endometrial vascularity (35.06 ± 2.56 mm2) than young (17.21 ± 1.26 mm2) and middle aged non-pregnant mares (23.84 ± 1.50 mm2) (p ≤ 0.05). We hypothesized that the higher blood flow area seen in older barren mares may be a consequence of a subclinical endometritis due to repeated flushing for embryo recovery. The results of the present study indicate that power Doppler ultrasound combined with computer assisted analysis of images are reliable techniques to detect early pregnancy prior to embryo recovery