Inappropriate sinus tachycardia in post-COVID-19 syndrome

Inappropriate sinus tachycardia (IST) is a common observation in patients with post-COVID-19 syndrome (PCS) but has not yet been fully described to date. To investigate the prevalence and the mechanisms underlying IST in a prospective population of PCS patients. Consecutive patients admitted to the PCS Unit between June and December 2020 with a resting sinus rhythm rate ≥ 100 bpm were prospectively enrolled in this study and further examined by an orthostatic test, 2D echocardiography, 24-h ECG monitoring (heart rate variability was a surrogate for cardiac autonomic activity), quality-of-life and exercise capacity testing, and blood sampling. To assess cardiac autonomic function, a 2:1:1 comparative sub-analysis was conducted against both fully recovered patients with previous SARS-CoV-2 infection and individuals without prior SARS-CoV-2 infection. Among 200 PCS patients, 40 (20%) fulfilled the diagnostic criteria for IST (average age of 40.1 ± 10 years, 85% women, 83% mild COVID-19). No underlying structural heart disease, pro-inflammatory state, myocyte injury, or hypoxia were identified. IST was accompanied by a decrease in most heart rate variability parameters, especially those related to cardiovagal tone: pNN50 (cases 3.2 ± 3 vs. recovered 10.5 ± 8 vs. non-infected 17.3 ± 10; p < 0.001) and HF band (246 ± 179 vs. 463 ± 295 vs. 1048 ± 570, respectively; p < 0.001). IST is prevalent condition among PCS patients. Cardiac autonomic nervous system imbalance with decreased parasympathetic activity may explain this phenomenon.

Therapeutic Potential of Vital Transcription Factors in Alzheimer’s and Parkinson’s Disease With Particular Emphasis on Transcription Factor EB Mediated Autophagy

Autophagy is an important cellular self-digestion and recycling pathway that helps in maintaining cellular homeostasis. Dysregulation at various steps of the autophagic and endolysosomal pathway has been reported in several neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington disease (HD) and is cited as a critically important feature for central nervous system (CNS) proteostasis. Recently, another molecular target, namely transcription factor EB (TFEB) has been explored globally to treat neurodegenerative disorders. This TFEB, is a key regulator of autophagy and lysosomal biogenesis pathway. Multiple research studies suggested therapeutic potential by targeting TFEB to treat human diseases involving autophagy-lysosomal dysfunction, especially neurodegenerative disorders. A common observation involving all neurodegenerative disorders is their poor efficacy in clearing and recycle toxic aggregated proteins and damaged cellular organelles due to impairment in the autophagy pathway. This dysfunction in autophagy characterized by the accumulation of toxic protein aggregates leads to a progressive loss in structural integrity/functionality of neurons and may even result in neuronal death. In recent years TFEB, a key regulator of autophagy and lysosomal biogenesis, has received considerable attention. It has emerged as a potential therapeutic target in numerous neurodegenerative disorders like AD and PD. In various neurobiology studies involving animal models, TFEB has been found to ameliorate neurotoxicity and rescue neurodegeneration. Since TFEB is a master transcriptional regulator of autophagy and lysosomal biogenesis pathway and plays a crucial role in defining autophagy activation. Studies have been done to understand the mechanisms for TFEB dysfunction, which may yield insights into how TFEB might be targeted and used for the therapeutic strategy to develop a treatment process with extensive application to neurodegenerative disorders. In this review, we explore the role of different transcription factor-based targeted therapy by some natural compounds for AD and PD with special emphasis on TFEB.

Observing impact of profession change on ‘habits of mind’: A factor oriented approach

A common observation in Transformative Learning (TL) literature is the scarcity of ways to gauge the extent of personal transformation. This is despite a recorded history of more than four decades and the existence of multiple schools of thought in TL. Also, there has been insufficient exploration of the personal transformation of profession changers in the TL space. We believe it is important to operationalize the key concepts of the TL theory through quantitative methods to make way for newer insights. In this paper, using the case of profession changers from India, we extend Mezirow’s work on six types of ‘Habits of Mind’ beyond their original conceptualization by identifying constituent latent factors. We examine and establish the reliability and validity of these factors and recommend a factor-based scale approach for application.

Glucagon Clearance is Preserved in Type 2 Diabetes

Hyperglucagonemia is a common observation in both obesity and type 2 diabetes, and the etiology is primarily thought to be hypersecretion of glucagon. We investigated whether altered elimination kinetics of glucagon could contribute to the hyperglucagonemia in type 2 diabetes and obesity<i>. </i>Individuals with type 2 diabetes and preserved kidney function (8 with and 8 without obesity) and matched control individuals (8 with and 8 without obesity) were recruited. Each participant underwent a 1-hour glucagon infusion (4 ng/kg/min), achieving steady-state plasma glucagon concentrations, followed by a 1-hour wash-out period. Plasma levels, the metabolic clearance rate (MCR), half-life (T_½) and volume of distribution of glucagon were evaluated and a pharmacokinetic model was constructed.<i> </i>Glucagon MCR and volume of distribution were significantly higher in the type 2 diabetes group compared to the control group, while no significant differences between the groups were found in glucagon T_½. Individuals with obesity had neither a significantly decreased MCR, T_½, nor volume of distribution of glucagon. In our pharmacokinetic model, glucagon MCR associated positively with fasting plasma glucose and negatively with body weight. In conclusion, our results suggest that impaired glucagon clearance is not a fundamental part of the hyperglucagonemia observed in obesity and type 2 diabetes.

Glucagon Clearance is Preserved in Type 2 Diabetes

Hyperglucagonemia is a common observation in both obesity and type 2 diabetes, and the etiology is primarily thought to be hypersecretion of glucagon. We investigated whether altered elimination kinetics of glucagon could contribute to the hyperglucagonemia in type 2 diabetes and obesity<i>. </i>Individuals with type 2 diabetes and preserved kidney function (8 with and 8 without obesity) and matched control individuals (8 with and 8 without obesity) were recruited. Each participant underwent a 1-hour glucagon infusion (4 ng/kg/min), achieving steady-state plasma glucagon concentrations, followed by a 1-hour wash-out period. Plasma levels, the metabolic clearance rate (MCR), half-life (T_½) and volume of distribution of glucagon were evaluated and a pharmacokinetic model was constructed.<i> </i>Glucagon MCR and volume of distribution were significantly higher in the type 2 diabetes group compared to the control group, while no significant differences between the groups were found in glucagon T_½. Individuals with obesity had neither a significantly decreased MCR, T_½, nor volume of distribution of glucagon. In our pharmacokinetic model, glucagon MCR associated positively with fasting plasma glucose and negatively with body weight. In conclusion, our results suggest that impaired glucagon clearance is not a fundamental part of the hyperglucagonemia observed in obesity and type 2 diabetes.

Mind the gap: From recommendation to practice in crisis management. Exploring the gap between the “lessons identified” during exercise cygnus and the UK government response to COVID-19

The failure to learn lessons from crises is a common observation. The UK Government has been criticized for its response to the COVID-19 crisis. Many critics have highlighted the Government’s apparent failure to learn the lessons from Exercise Cygnus, which made recommendations to improve the UK’s response to a pandemic. This article compares and contrasts the UK Government’s response with the exercise recommendations. It critiques the gaps using current crisis management literature and argues that to avoid future failings, more emphasis is needed on the effectiveness of recommendations from exercises. If this is not done, exercise lessons identified, and their recommendations will not be operationalized. This article argues that the successful transition from policy recommendation to practice requires recommendations to be contextualized, so they are feasible and practical, before they can be institutionalized. It introduces a practical framework and organizational actions on how future exercises can close the gap from lessons identified to be learned and shape practice.

The Development of Ecchymosis after Administration of Convalescent Serum in a Patient with COVID-19 Associated with Thrombocytosis

COVID-19 can have an unpredictable and severe course, leading to many hypotheses regarding its pathophysiology and clinical manifestations. Haematological manifestations are a significant predictor of disease severity. The most common observation is lymphopenia with an increased neutrophil:lymphocyte ratio. Platelets have been implicated in thrombogenic events, but the most frequently reported abnormality is mild thrombocytopenia.<br /> Here we present an interesting case of a patient with moderate COVID-19 who presented with cutaneous ecchymoses and thrombocytosis, and discuss this paradox.

If you've earned it, you deserve it: ultimatums, with Lego

The ultimatum and dictator games were developed to help identify the fundamental motivators of human behavior, typically by asking participants to share windfall endowments with other persons. In the ultimatum game, a common observation is that proposers offer, and responders refuse to accept, a much larger share of the endowment than is predicted by rational choice theory. However, in the real world, windfalls are rare: money is usually earned. I report here a small study aimed at testing how participants react to an ultimatum game after they have earned their endowments by either building a Lego model or spending some time sorting out screws by their length. I find that the shares that proposers offer and responders accept are significantly lower than that typically observed with windfall money, an observation that is intensified when the task undertaken to earn the endowment is generally less enjoyable and thus perhaps more effortful (i.e., screw sorting compared to Lego building). I suggest, therefore, that considerations of effort-based desert are often important drivers behind individual decision-making, and that laboratory experiments, if intended to inform public policy design and implementation, ought to mirror the broad characteristics of the realities that people face.

Practical Wisdom and Honesty

The previous chapter focused on the motivational side of the virtue of honesty. But moral virtues are normally understood to consist of more than just motivational states. Virtuous thoughts of various kinds, for instance, play a role, and honesty is no exception. Here is another common observation about moral virtues: they are connected in some way to practical wisdom. This has long been held by Aristotelian approaches in particular, and it is important to clarify what relationship, if any, practical wisdom bears to honesty. Hence the goal of this chapter is to explore the role of virtuous thoughts and practical wisdom with respect to the virtue of honesty.

Problems of empirical solutions to the theory-ladenness of observation

Recent years have seen enticing empirical approaches to solving the epistemological problem of the theory-ladenness of observation. I group these approaches in two categories according to their method of choice: testing and refereeing. I argue that none deliver what friends of theory-neutrality want them to. Testing does not work because both evidence from cognitive neuroscience and perceptual pluralism independently invalidate the existence of a common observation core. Refereeing does not work because it treats theory-ladenness as a kind of superficial, removable bias. Even if such treatment is plausible, there is likely no method to ascertain that effects of this bias are not present. More importantly, evidence from cognitive neuroscience suggests that a deeper, likely irremovable kind of theory-ladenness lies within the perceptual modules.