A Tale of Two States: Pluripotency Regulation of Telomeres.

Inside the nucleus, chromatin is functionally organized and maintained as a complex three-dimensional network of structures with different accessibility such as compartments, lamina associated domains, and membraneless bodies. Chromatin is epigenetically and transcriptionally regulated by an intricate and dynamic interplay of molecular processes to ensure genome stability. Phase separation, a process that involves the spontaneous organization of a solution into separate phases, has been proposed as a mechanism for the timely coordination of several cellular processes, including replication, transcription and DNA repair. Telomeres, the repetitive structures at the end of chromosomes, are epigenetically maintained in a repressed heterochromatic state that prevents their recognition as double-strand breaks (DSB), avoiding DNA damage repair and ensuring cell proliferation. In pluripotent embryonic stem cells, telomeres adopt a non-canonical, relaxed epigenetic state, which is characterized by a low density of histone methylation and expression of telomere non-coding transcripts (TERRA). Intriguingly, this telomere non-canonical conformation is usually associated with chromosome instability and aneuploidy in somatic cells, raising the question of how genome stability is maintained in a pluripotent background. In this review, we will explore how emerging technological and conceptual developments in 3D genome architecture can provide novel mechanistic perspectives for the pluripotent epigenetic paradox at telomeres. In particular, as RNA drives the formation of LLPS, we will consider how pluripotency-associated high levels of TERRA could drive and coordinate phase separation of several nuclear processes to ensure genome stability. These conceptual advances will provide a better understanding of telomere regulation and genome stability within the highly dynamic pluripotent background

Volume of exercise in patients admitted for decompensated heart failure

Decompensated Heart Failure (HF) patients have a significant functional dependence, impairment of performance in activities of daily living and low exercise tolerance. Exercise is a well establish cardiac rehabilitation intervention which leads to improvement of symptoms. The amount of Exercise is directly related to its benefits. Purpose: To evaluate the volume of exercise that HF patients preform during the hospitalization Methods: 50 patients performed an aerobic exercise training program (ERIC-HF: Early rehabilitation in cardiology – heart failure) with 5 sequential stages: respiratory training, cyclo ergometer for 5 to 10 min, walking training for 5 to 10 min and then for 10 to 15 min and walking training for 10 to 15 min followed by 5 min climbing stairs. The patient progresses on the program according to his synthons and nurse clinical judge. The volume of exercise is registered in number of turns on the cyclo ergometer, meters walked, number of steps and the amount of time they spent exercising. Subjective perception of exertion using Borg scale, and vital signs are evaluated in every training session (twice a day for 5 days a week). At discharge patients preform a 6 minute walking test (6MWT). Results: Patients performed 683 sessions of exercise with an average of 14 sessions each, for 16 (±9) days of hospitalization. Patients performed progressive periods of exercise, for more time and with lower levels of perceived exertion, presenting an average value of 6 (±3) in the admission and 2(±2) at the discharge day. 27 patients reached the final stage of the program (climbing stairs) with an average of 87 steps in 5 minutes. The patients who performed a bigger volume of Exercise walked more distance in the 6MWT: 293 (±87) meters compared with patients who didn´t performed stairs: 245 (±31) Conclusions: AET can be well tolerated by patients admitted due to decompensated HF and patients who are capable to perform a bigger volume of exercise can improve much more their functional capacity showed by the 6MWT results.info:eu-repo/semantics/publishedVersio

Exercise for heart failure inpatients: ERIC­HF programe

Decompensated Heart Failure (HF) patients are often characterized by dyspnea, fatigue, edema, functional dependence and impairment of performance in activities of daily living (ADL). Aerobic exercise training (AET) is a well establish cardiac rehabilitation intervention which leads to improvement of symptoms, promotes the functional capacity of the patients and even an increase of exercise tolerance. Although the benefits, exercise is not yet validated for inpatients during the phase of stabilization. Purpose: To evaluate the feasibility and safety of an AET program for patients admitted due to decompensated HF: ERIC-HF program Methods: Patients are randomized in training group (TG) or control (CG). Data include cardiovascular history, HF history and two functional tools: London Chest of Daily Living Activities (LCADL) and Barthel Index (BI). TG patients performed the ERIC-HF program twice a day for 6 days per week. ERIC-HF program is a supervised AET program, with increasing levels of intensity, divided into 5 stages (respiratory training, gait training and climbing stairs, for progressive duration periods). Vital signs are evaluated before and immediately after the exercise, as well as the Borg Modified Perceived Exertion. CG patients performed physical activity in accordance with their preference, always supervised too . At discharge, all patients perform a six-minute walking test (6MWT) and evaluation of LCADL and BI. Results: 100 patients were randomized (50 in each group) with na average of age of 71 (±11) years old, 61 are male, 80% are in NYHA class III. At admission, both groups have the same level of functional dependence. TG patients performed a global amount of 573 sessions of exercise. At discharge, TG patients presented lower LCADL score, higher BI score and a 54 meters difference on the 6MWT (statistically significant) which represents a better functional capacity. Absense of adverse events like falls, precordial pain or worsening of clinical state. Conclusions: ERIC-HF program is safe and promotes functional capacity. We can also conclude that probably AET is safe and viable, for this kind of patients. No other study of our knowledge, has demonstrated this findings.info:eu-repo/semantics/publishedVersio

Exploring factors related to good exercise capacity in patients undergoing ERIC-HF program

Decompensated Heart Failure (HF) patients are characterized by functional dependence and low exercise capacity. The factors associated to a good response to exercise are still unexplored. The ERIC-HF program is an aerobic exercise training program developed for HF inpatients and includes cycloergometer training, walking and climbing stairs in order to promote patient’s functional capacity during the in-hospital stay period. Purpose: to identify the factors related to good response to an aerobic exercise training program for decompensated heart failure (HF) patients. Methods: Cross-sectional study with 143 inpatients who performed the ERIC-HF program. Functional capacity was evaluated using three different tools: the London Chest of Activity of Daily Living (LCADL) scale, the Barthel Index (BI) and the 6-minute walking test (6MWT). A good response to the program was defined as a ≥ 300 meters distance at the 6MWT at discharge. Univariate analysis was performed between patients who walked 300 meters or more at the 6MWT and patients who walked less than 300meters, using Chi-square tests and Student’s T-test. Logistic regression analysis was performed to describe factors that were independently related to better functional capacity at discharge. Variables with a p-value smaller than 0.15 in the univariate analyses were entered into the logistic regression. A significance level at p <0.05 was assumed. The dependent variables were: 1) distance walked at the 6MWT, 2) the change between admission-to-discharge scores of BI and 3) LCADL. Independent variables were: 1) gender, 2) age, 3) number of exercise sessions, 4) number of days of in-hospital stay, 5) BIad, 6) LCADLad, 7) NYHA functional class, 8) left ventricular ejection fraction (LVEF) and 9) etiology. Results: The mean age of the patients was 67 (±10) years, 15.4% were NYHA class IV and 80% had reduced ejection fraction. The aetiology of HF was similar between ischaemic disease (32.9%) and valvular (33.6%). Patients presented a high level of impairment on FC. The majority were male (97; 67.8%), with an average of three CVRF and mostly sedentary, with only 17% performing regular physical activity. There was no significant difference between etiologies of HF. Comparison between the group of patients who walked 300meters or more, at the 6MWT, and patients who walked less than 300metrs, showed statistically significant differences in terms of gender, age, BI, LCADL, etiology of HF and LVEF. After logistic regression, age (p = 0.002), gender (p = 0.001) and BI (p<0.000) at admission showed to be statistically significant factors that affect the distance walked. Conclusions: The ERIC-EF programe appears to be more effective in male, younger patients and with low FC at admission. Apparently, reduced ejection fraction does not interfere with progression during the programe. Gender influences the performance of patients, since men presented with higher FC at discharge.info:eu-repo/semantics/publishedVersio

Volume of exercise in patients admitted for decompensated heart failure

Decompensated Heart Failure (HF) patients have a significant functional dependence, impairment of performance in activities of daily living and low exercise tolerance. Exercise is a well establish cardiac rehabilitation intervention which leads to improvement of symptoms. The amount of Exercise is directly related to its benefits. Purpose: To evaluate the volume of exercise that HF patients preform during the hospitalization Methods: 50 patients performed an aerobic exercise training program (ERIC-HF: Early rehabilitation in cardiology – heart failure) with 5 sequential stages: respiratory training, cyclo ergometer for 5 to 10 min, walking training for 5 to 10 min and then for 10 to 15 min and walking training for 10 to 15 min followed by 5 min climbing stairs. The patient progresses on the program according to his synthons and nurse clinical judge. The volume of exercise is registered in number of turns on the cyclo ergometer, meters walked, number of steps and the amount of time they spent exercising. Subjective perception of exertion using Borg scale, and vital signs are evaluated in every training session (twice a day for 5 days a week). At discharge patients preform a 6 minute walking test (6MWT). Results: Patients performed 683 sessions of exercise with an average of 14 sessions each, for 16 (±9) days of hospitalization. Patients performed progressive periods of exercise, for more time and with lower levels of perceived exertion, presenting an average value of 6 (±3) in the admission and 2(±2) at the discharge day. 27 patients reached the final stage of the program (climbing stairs) with an average of 87 steps in 5 minutes. The patients who performed a bigger volume of Exercise walked more distance in the 6MWT: 293 (±87) meters compared with patients who didn´t performed stairs: 245 (±31) Conclusions: AET can be well tolerated by patients admitted due to decompensated HF and patients who are capable to perform a bigger volume of exercise can improve much more their functional capacity showed by the 6MWT results.info:eu-repo/semantics/publishedVersio

Who are the best decompensated heart failure inpatient responders to aerobic exercise trainning?

Exercise training is an excellent tool to promote functional capacity in chronic heart failure (HF) patients. Although its benefits in this population, it needs to be demonstrated in decompensated HF patients. A way to optimize an intervention is to evaluate who are the good responders and understand the causes of no response. Knowing the factors of good response is also important to emphasize the feasibility of an intervention and to deliver it to the ones who get the most benefit of it. Purpose To identify the characteristics that lead a patient to have a better response to an aerobic exercise training program for decompensated HF inpatients – ERICHF (early rehabilitation in cardiology – heart failure) Methods 50 patients who performed ERICHF program (clinicaltrials.gov, Identifier: NCT03838003) during the phase of stabilization were evaluated in terms of their sociodemographic, functional and physiological characteristics and performance during the program. The main variable used to understand the performance of the patients was the variation of the distance walked in the 6minute walking test (6MWT), performed as soon as the patient was able to do it (6MWTinitial) and at discharge (6MWTdischarge). A multivariate linear regression with stepwise algorithm and Durbin Watson test were used in order to determine which variables are related to a better variation on the 6MWT, namely: age, LCADL and Barthel index scores at admission and discharge, number of days of hospitalization, number of cardiovascular risk factors, NYHA class, etiology of HF and ventricular function. It was assumed a significance level at p<0.05. Results: Patient’s average age was 71 (±11) years old, 34 are male, 80% are in NYHA class III and 73% have severe left ventricular depression. Patients present a median of 76 points in BI at admission (minimum of 45 and maximum of 97) and a median of 32 at LCADL (minimum of 24 and maximum of 45 points). The mean distance walked in the 6MWTinicial performed by the patients was 199,9 (±115,9) meters and 287,6 (±128,9) eters at 6MWTdischarge, representing a 87,7 (±170,6) meters difference. According to the lin ear regression an equation was obtained: Difference of the 6MWT = 454,6941* 6MWTinitial+2,981*Barthelinitial5,554* age. This equation explains 65% of the variation of the model in this sample of patients. Using this variables it’s possible to predict how much distance a patient will walk at the end of the rehabilitation program, and understand the predicted performance in the program. Conclusions Patients with lower functional capacity evaluated by 6MWT, but with higher BI scores and youngest, are the ones who probably will have the most significant results from the rehabilitation program.info:eu-repo/semantics/publishedVersio

Exercise for decompensated heart failure inpatients – ERIC-HF program

Decompensated Heart Failure (HF) patients are often characterized by dyspnea, fatigue, edema, functional dependence and impairment of performance in activities of daily living (ADL). Aerobic exercise training (AET) is a well establish cardiac rehabilitation intervention which leads to improvement of symptoms, promotes the functional capacity of the patients and even an increase of exercise tolerance. Although the benefits, exercise is not yet validated for inpatients during the phase of stabilization. Purpose: To evaluate the feasibility and safety of an AET program for patients admitted due to decompensated HF: ERIC-HF program Methods: Patients are randomized in training group (TG) or control (CG). Data include cardiovascular history, HF history and two functional tools: London Chest of Daily Living Activities (LCADL) and Barthel Index (BI). TG patients performed the ERIC-HF program twice a day for 6 days per week. ERIC-HF program is a supervised AET program, with increasing levels of intensity, divided into 5 stages (respiratory training, gait training and climbing stairs, for progressive duration periods). Vital signs are evaluated before and immediately after the exercise, as well as the Borg Modified Perceived Exertion. CG patients performed physical activity in accordance with their preference, always supervised too . At discharge, all patients perform a six-minute walking test (6MWT) and evaluation of LCADL and BI. Results: 100 patients were randomized (50 in each group) with na average of age of 71 (±11) years old, 61 are male, 80% are in NYHA class III. At admission, both groups have the same level of functional dependence. TG patients performed a global amount of 573 sessions of exercise. At discharge, TG patients presented lower LCADL score, higher BI score and a 54 meters difference on the 6MWT (statistically significant) which represents a better functional capacity. Absense of adverse events like falls, precordial pain or worsening of clinical state. Conclusions: ERIC-HF program is safe and promotes functional capacity. We can also conclude that probably AET is safe and viable, for this kind of patients. No other study of our knowledge, has demonstrated this findings.info:eu-repo/semantics/publishedVersio

Characteristics of good response to aerobic axercise training in decompensated heart failure patients

Exercise training is an excellent tool to promote functional capacity in chronic heart failure (HF) patients. Although its benefits in this population, it needs to be demonstrated in decompensated HF patients. A way to optimize an intervention is to evaluate who are the good responder and understand the causes of no response. Knowing the factors of good response is also important to emphasize the feasibility of an intervention and to deliver it to the ones who get the most benefit of it. Purpose To identify the characteristics that lead a patient to have a better response to an aerobic exercise training program for decompensated HF inpatients – ERICHF (early rehabilitation in cardiology – heart failure) Methods 50 patients who performed ERICHF program during the phase of stabilization were evaluated in terms of their sociodemographic, functional and physiological characteristics and performance during the program. The main variable used to understand the performance of the patients was the variation of the distance walked in the 6minute walking test (6MWT), performed as soon as the patient were able to do it (6MWTinicial) and at discharge (6MWTdischarge). A multiple linear regression was made in order to determine which variables are related to a better variation on the 6MWT, namely: age, LCADL and Barthel index (BI) scores at admission and discharge, number of days of hospitalization, number of cardiovascular risk factors, NYHA class, etiology of HF and ventricular function. DurbinWatson test was used to analyze the existence of independence of residual random variables. It was assumed a significance level at p<0.05. Results: Patient’s average age was 71 (±11) years old, 34 are male, 80% are in NYHA class III and 73% have severe left ventricular depression. Patients present a median of 76 points in BI at admission (minimum of 45 and maximum of 97) and a median of 32 at LCADL (minimum of 24 and maximum of 45 points). The mean distance walked in the 6MWTinicial performed by the patients was 199,9 (±115,9) meters and 287,6 (±128,9) meters at 6MWTdischarge, representing a 87,7 (±170,6) meters variation. According to the linear regression, an equation was obtained: Difference of the 6MWT = 454,6941* 6MWTinitial+2,981*Barthelinitial5,554* age. This equation explains 65% of the variation of the model in this sample of patients. Using this variables it’s possible to know how much distance a patient can walk, and understand if he is going to have a good performance in the program. Conclusions Patients with the worst results in the initial 6MWT, higher initial Barthel and younger ages, will get the most gains in terms of difference walked between the initial and final 6MWT and have the most benefit from the intervention program.info:eu-repo/semantics/publishedVersio

ERICHF program (early rehabilitation in cardiology heart failure) pilot study

Decompensated Heart Failure (HF) patients are often characterized by functional dyspnea, fatigue, edema, functional dependence and impairment of performance in activities of daily living. Aerobic exercise training (AET) is a well establish cardiac rehabilitation intervention which improves symptoms, promotes the functional capacity and even increase exercise tolerance. Although the benefits, exercise is not yet validated for inpatients during the phase of stabilization. Purpose: To evaluate the feasibility and safety of an AET program for patients admitted due to decompensated HF: ERICHF (Early Rehabilitation in Cardiology – Heart Failure) program Methods: Pilot randomized controlled singleblind trial Patients are randomized in training group (TG) or control group (CG). Data include cardiovascular history, HF history and two functional tools: London Chest of Daily Living Activities (LCADL) and Barthel Index (BI). TG patients performed the ERICHF program twice a day for 5 days per week. ERICHF program is a supervised AET program, with increasing levels of intensity, divided into 5 stages (respiratory training, cycloergometer training, gait training and climbing stairs, for progressive duration periods). Vital signs were evaluated before and immediately after the exercise, as well as the Borg Modified Perceived Exertion. CG patients performed physical activity in accordance with the guidelines available for inpatients, always supervised too. A sixminute walking test (6MWT) was performed as soon as patients are able to do it. At discharge, all patients perform another 6MWT, as so as evaluation of LCADL and BI. Results: 114 patients were randomized (64 in TG and 50 in CG) with an average of age of 72 (±9) years old, 70 are male, 82% are in NYHA class III. At admission, both groups have the same level of functional dependence according to LCADL (31 vs 32) and Barthel (73 vs 73) scores. TG patients performed 932 sessions of exercise, with an average of 17 sessions each, for 15 (±9) days of hospitalization. There is a difference of 83 meters between the two 6MWT performed by TG patients, which demonstrates clinical significance. At discharge, TG patients presented lower LCADL score (12 vs 16, p=0,006), higher BI (98 vs 92, p=0,038) score and a 64 meters difference on the 6MWT (p=0,0032) which represents a better functional capacity. There were absence of adverse events like falls, precordial pain, malignant arrhythmias and worsening of clinical state Conclusions: ERICHF program demonstrated, in this sample of patients, to be safe and to promote functional capacity. We can also infer that probably AET is safe and viable, for this kind of patients, related to the absence of adverse events. No other study of our knowledge has demonstrated this findings.info:eu-repo/semantics/publishedVersio

Narrativas publicitárias nas redes sociais: a mudança de paradigma das práticas criativas das agências portuguesas de comunicação

Dissertação de mestrado em Marketing e EstratégiaO fenómeno das redes sociais tem permitido às marcas usarem também este meio para comunicarem com o consumidor, nomeadamente através de técnicas publicitárias. Contudo, nem sempre as marcas sabem criar e desenvolver as suas campanhas de comunicação com narrativas publicitárias nas redes sociais, uma vez que estas redes possuem caraterísticas muito específicas como a necessidade quase imediata de uma comunicação bidirecional entre marca e consumidor, onde este urge de respostas rápidas num espaço onde a propagação da informação tem um alcance muito grande, bem como a adaptação às narrativas que este espaço coloca às pessoas, dado que a questão tempo assume um papel preponderante onde as histórias têm de se prolongar no tempo. Considerando estas mudanças no meio privilegiado de comunicação publicitária, encontra-se um gap que consiste em perceber se as práticas criativas nas redes sociais se adequam a essa mudança de paradigma que as narrativas publicitárias devem conter. O objetivo deste estudo consiste em identificar junto de agências de publicidade portuguesas novas práticas criativas nas redes sociais, assim como identificar os desafios e obstáculos para os profissionais dessas agências. Através de quinze entrevistas semiestruturadas em profundidade, percebe-se que as marcas têm vindo a mudar a sua comunicação recorrendo a várias práticas e formatos com maior engagement, como é o caso do storytelling e dos videocast. Com o aparecimento do digital e das redes sociais o contexto mudou, os consumidores assumem um papel preponderante na comunicação podendo escolher de forma interativa o enredo e desfecho das histórias. Assiste-se a um contexto humano no qual é exigido às agências uma capacidade elevada para criar histórias que chamem à atenção dos consumidores e que permitam às marcas, com recurso a novos formatos, ultrapassar o principal desafio que lhes é colocado da visibilidade, de se destacarem das restantes marcas e conseguirem um espaço na mente dos consumidores, bem como o obstáculo inerente à imprevisibilidade do comportamento dos consumidores. Com esta investigação sobre as narrativas publicitárias nas redes sociais, focando a mudança de paradigma das práticas criativas das agências de publicidade portuguesas, mostra-se como a mudança de paradigma está a afetar as práticas criativas dos publicitários descrevendo os principais obstáculos e desafios nesta matéria.The social media phenomenon has allowed brands to use this means to communicate with the consumer and advertise their name. However, brands do not always know how to create and develop their own communication campaigns with advertising storylines in social media. Said media tends to have very specific characteristics, such as the need to have an immediate, bidirectional communication between the brand and the consumer, where answers must be given in a short amount of time in a setting of wide range of information spread, or the adaptation to these advertising storylines, once time assumes a preponderant role given these stories have to extend themselves through time. Considering these changes in the privileged means of advertising, there is a gap that consists on trying to understand if these creative practices in the social media are adequate to this shift of paradigm that advertising stories should contain. The objective of this study is to identify, alongside Portuguese advertising agencies, new creative practices to use in social media, as well as identifying the challenges and obstacles that their employees face. Through fifteen in-depth interviews, it was possible to understand that brands have been changing their communication methods using various practices and formats with more engagement, as is the case of storytelling and videocasting. With the emergence of digital and social media the context has changed: the consumers play a key role in the communication, as they are able to interactively select the plot and the outcome of the stories. We are witnessing a human context in which agencies are required to have a well-versed ability to create stories that draw the attention of consumers and that enable brands, by making use of new formats, to overcome the main challenges that they are faced with: stand out from other brands and conquer a place in consumers’ minds, as well as the obstacles inherent to the unpredictability of their behaviour. With this research on advertising narratives in social media, focusing on the changing paradigm of creative practices of the Portuguese advertising agencies, it is possible to show that this shift is affecting the creative practices of advertisers, and identify the main obstacles and challenges in this matter