Potential Prion Involvement in Long COVID-19 Neuropathology, Including Behavior.

Prion' is a term used to describe a protein infectious particle responsible for several neurodegenerative diseases in mammals, e.g., Creutzfeldt-Jakob disease. The novelty is that it is protein based infectious agent not involving a nucleic acid genome as found in viruses and bacteria. Prion disorders exhibit, in part, incubation periods, neuronal loss, and induce abnormal folding of specific normal cellular proteins due to enhancing reactive oxygen species associated with mitochondria energy metabolism. These agents may also induce memory, personality and movement abnormalities as well as depression, confusion and disorientation. Interestingly, some of these behavioral changes also occur in COVID-19 and mechanistically include mitochondrial damage caused by SARS-CoV-2 and subsequenct production of reactive oxygen species. Taken together, we surmise, in part, long COVID may involve the induction of spontaneous prion emergence, especially in individuals susceptible to its origin may thus explain some of its manesfestions post-acute viral infection.

A Review Article on Exercise Intolerance in Long COVID: Unmasking the Causes and Optimizing Treatment Strategies.

There is a growing body of research on SARS-CoV-2 (PASC), previously known as the post-COVID syndrome, a chronic condition characterized by symptoms that persist after SARS-CoV-2 infection. Among these symptoms, feelings of physical exhaustion and prolonged fatigue are particularly prevalent and can significantly impact patients' quality of life. These symptoms are associated with reduced overall physical capacity, decreased daily physical activity, malaise after intense training, and intolerance to physical activity (IFA). IFA, described as a reduced ability to perform physical activities typical for the patient's age, can often lead to a sedentary lifestyle. Prolonged physical inactivity can cause deterioration in the overall physical condition and disrupt mitochondrial function, triggering a vicious cycle of gradual symptom worsening. The underlying causes of PASC remain unclear; however, several biochemical mechanisms have been discussed to explain the body's energy depletion, and a multidisciplinary approach that combines physical and cognitive rehabilitation and lifestyle interventions such as exercise and diet modifications has been suggested to improve the overall health and well-being of PASC patients. This critical review aims to review the existing research on the possible causes and links among chronic fatigue, reduced physical activity, and exercise intolerance in patients with PASC. Further research into the underlying causes and treatment of PASC and the importance of developing individualized treatment is needed to address each patient's unique health requirements.

The Updating and Individualizing of Sleep Hygiene Rules for Non-clinical Adult Populations.

Sleep hygiene is essential for the prevention of somatic and mental disorders, including the prevention of sleep disorders. However, it does not typically address individual differences. The aim of this review is threefold: first, to outline the empirical evidence for particular components of sleep hygiene rules; second, to indicate the importance of individualized sleep hygiene application with regard to the varying degree of validity of sleep hygiene rules in the population; third, to highlight a new field of sleep hygiene, namely light hygiene. PubMed and Google Scholar were used to identify studies that were published between 2007 and 2022. A search was conducted for studies related to sleeping rules topics: sleep regularity, regular exercise, alcohol, caffeine, napping, relaxation and meditation, food intake and light exposure. In applying these sleep hygiene principles, it is essential to pay attention to individual variables such as age, genetic predisposition, health status, and substance (caffeine, alcohol) possible dependence.

Attention-Deficit/Hyperactivity Disorder (ADHD) and Time Perception in Adults: Do Adults with Different ADHD Symptomatology Severity Perceive Time Differently? Findings from the National Czech Study.

BACKGROUND Studies show neurological differences between patients with attention-deficit/hyperactivity disorder (ADHD) and healthy controls. Furthermore, it is possible that poor timing is linked with impairments in neural circuitry. This study aimed to test the hypothesis that there is a difference in time perception between adults with severe ADHD symptomatology and adults with no ADHD symptomatology. MATERIAL AND METHODS Previously, we collected data from a more extensive set of participants (n=1518) concerning the prevalence of ADHD in adulthood. We recruited participants from 3 groups defined by increasing ADHD severity out of this participant pool. Each participant was presented with 2 experimental tasks (in counterbalanced order): duration estimation and duration discrimination. RESULTS In general, we did not find any specific differences in time perception related to the severity of ADHD. Regarding duration estimation, we found that the difference between the actual and estimated durations increased with the actual duration (F(1, 7028.00)=2685.38, P<0.001). Although the differences between groups were not significant, the group×duration interaction was (F[1, 7028.00]=10.86, P<0.001), with a very small effect size (ηp²<0.001, 95% CI [0.00, 0.01]). CONCLUSIONS The results suggest that although individuals may demonstrate increased ADHD symptomatology, they may not have objectively more significant difficulties in time perception tasks than their counterparts with mild symptomatology. Nonetheless, time perception should be further studied because, as qualitative research suggests, participants with more severe ADHD symptomatology subjectively perceive more significant differences in time management in real life.

Cognitive and Socioemotional Development at 5 and 9 Years of Age of Children Born with Very Low Birth Weight and Extremely Low Birth Weight in the Czech Republic.

BACKGROUND There is a high prevalence of cognitive and socioemotional dysfunction in very low birth weight (VLBW <1500 g) and extremely low birth weight (ELBW <1000 g) children. This study from the Czech Republic aimed to compare the cognitive and socioemotional development at 5 and 9 years of age of children born with VLBW/ELBW with children born with normal birth weight (NBW ≥2500 g). MATERIAL AND METHODS The clinical group consisted of 118 VLBW/ELBW children and the control group consisted of 101 children with NBW at ages 5 to 9 years. The research battery included selected subscales from the Intelligence and Development Scales (IDS), A Developmental Neuropsychological Assessment - second edition (NEPSY-II), and the Behavior Rating Inventory of Executive Function (BRIEF). Data were analyzed using STATA IC v. 15 software and G*Power (descriptive statistic, analysis of variance (ANOVA), correlations, multivariate analysis of variance - MANOVA, post hoc power analysis). RESULTS We found a statistically significant difference in cognitive and socioemotional development between children with VLBW/ELBW and those with NBW. The average intelligence quotient (IQ) of VLBW/ELBW children was 96.38, while that of NBW children was 12.98 points higher (P<0.001). NBW children achieved better results on all subtests of the IDS (P<0.001) as well as in affect recognition (P<0.001). All results for both groups were within normal range. Parents of VLBW/ELBW children did not recognize impaired executive functioning (P=0.494). CONCLUSIONS This study has shown significant cognitive and socioemotional deficit in children born with VLBW and ELBW when evaluated at 5 and 9 years of age.

Selective Neuronal Mitochondrial Targeting in SARS-CoV-2 Infection Affects Cognitive Processes to Induce 'Brain Fog' and Results in Behavioral Changes that Favor Viral Survival.

Alterations in brain functioning, especially in regions associated with cognition, can result from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and are predicted to result in various psychiatric diseases. Recent studies have shown that SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) can directly or indirectly affect the central nervous system (CNS). Therefore, diseases associated with sequelae of COVID-19, or 'long COVID', also include serious long-term mental and cognitive changes, including the condition recently termed 'brain fog'. Hypoxia in the microenvironment of select brain areas may benefit the reproductive capacity of the virus. It is possible that in areas of cerebral hypoxia, neuronal cell energy metabolism may become compromised after integration of the viral genome, resulting in mitochondrial dysfunction. Because of their need for constant high metabolism, cerebral tissues require an immediate and constant supply of oxygen. In hypoxic conditions, neurons with the highest oxygen demand become dysfunctional. The resulting cognitive impairment benefits viral spread, as infected individuals exhibit behaviors that reduce protection against infection. The effects of compromised mitochondrial function may also be an evolutionary advantage for SARS-CoV-2 in terms of host interaction. A high viral load in patients with COVID-19 that involves the CNS results in the compromise of neurons with high-level energy metabolism. Therefore, we propose that selective neuronal mitochondrial targeting in SARS-CoV-2 infection affects cognitive processes to induce 'brain fog' and results in behavioral changes that favor viral propagation. Cognitive changes associated with COVID-19 will have increasing significance for patient diagnosis, prognosis, and long-term care.

Interoception, Trait Anxiety, and the Gut Microbiome: A Cognitive and Physiological Model.

Trait anxiety is characterized as a constant and often subliminal state that persists during daily life. Interoception is the perception of internal states and sensations, including from the autonomic nervous system. This review aims to develop a predictive model to explain the emergence, manifestations, and maintenance of trait anxiety. The model begins with the assumption that anxiety states arise from active interoceptive inference. The subsequent activation of autonomic responses results from aversive sensory encounters. A cognitive model is proposed for trait anxiety that includes the aversive sensory components from interoception, exteroception, and proprioception. A further component of the hypothesis is that repeated exposure to subliminal anxiety-evoking sensory elements can lead to an overgeneralization of this response to other inputs that are generally non-aversive. Increased uncertainty may result when predicting the sensory environment, resulting in arbitrary interoceptive anxiety responses that may be due to unjustifiable causes. Arbitrary successful or unsuccessful matching of predictions and responses reduces the individual's confidence to maintain the anxiety trait. In this review, the application of the proposed model is illustrated using gut microbial dysbiosis or imbalance of the gut microbiome.

Time Perception is a Focal Symptom of Attention-Deficit/Hyperactivity Disorder in Adults.

Attention-Deficit/Hyperactivity Disorder (ADHD) is classically associated with symptoms that include inattentiveness, hyperactivity, and impulsivity together with a variety of other observable externalized symptoms. ADHD has also been associated with specific internalized cognitive symptoms, including restlessness and emotional impulsivity. This disorder has been recognized as a lifelong condition and can be recognized by a variety of unique cognitive phenomena. In addition to the frequently ignored affective symptoms exhibited by individuals diagnosed with ADHD, problems with time perception have been noted, although these are considered to be secondary issues. Temporal shifts in cognitive processing, however, may be at the very root of ADHD-related symptoms, given the importance of coordinated signal translation in the construction of behavior. In this review, we consider the evidence that suggests that differences in time perception are a central symptom in adults with ADHD. Some of these differences include the feeling of time moving faster, which causes difficulties in prospective time tasks and inaccuracies in time estimation tasks. We analyze the literature from both neurological and psychological perspectives and include an assessment of tools that can be administered via computer to measure time perception. We also suggest several computer-based methods that might be used to address problems with time perception in both children and adults. We strongly recommend the inclusion of ADHD symptoms associated with time perception in the next revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM) published by the American Psychiatric Association.

Editorial: The Pathogenesis of Long-Term Neuropsychiatric COVID-19 and the Role of Microglia, Mitochondria, and Persistent Neuroinflammation: A Hypothesis.

Persistent comorbidities occur in patients who initially recover from acute coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 'Long COVID' involves the central nervous system (CNS), resulting in neuropsychiatric symptoms and signs, including cognitive impairment or 'brain fog' and chronic fatigue syndrome. There are similarities in these persistent complications between SARS-CoV-2 and the Ebola, Zika, and influenza A viruses. Normal CNS neuronal mitochondrial function requires high oxygen levels for oxidative phosphorylation and ATP production. Recent studies have shown that the SARS-CoV-2 virus can hijack mitochondrial function. Persistent changes in cognitive functioning have also been reported with other viral infections. SARS-CoV-2 infection may result in long-term effects on immune processes within the CNS by causing microglial dysfunction. This short opinion aims to discuss the hypothesis that the pathogenesis of long-term neuropsychiatric COVID-19 involves microglia, mitochondria, and persistent neuroinflammation.

Psychiatric Manifestations of COVID-19 and Their Social Significance.

Alterations in complex behavioral patterns during the extended period of the COVID-19 pandemic are predicted to promote a variety of psychiatric disease symptoms due to enforced social isolation and self-quarantine. Accordingly, multifaceted mental health problems will continue to increase, thereby creating a challenge for society and the health care system in general. Recent studies show that COVID-19 can directly or indirectly influence the central nervous system, potentially causing neurological pathologies such as Alzheimer disease and Parkinson disease. Thus, chronic COVID-19-related disease processes have the potential to cause serious mental illnesses, including depression, anxiety, and sleep disorders. Importantly, mental health problems can foster systemic changes in functionally-linked neuroendocrine conditions that heighten a person's susceptibility to COVID-19 infection. These altered defense mechanisms may include compromised "self-control" and "self-care", as well as a "lack of insight" into the danger posed by the virus. These consequences may have serious social impacts on the future of COVID-19 survivors. Compounding the functionally related issues of altered mental health parameters and viral susceptibility are the potential effects of compromised immunity on the establishment of functional herd immunity. Within this context, mental health takes on added importance, particularly in terms of the need to increase support for mental health research and community-based initiatives. Thus, COVID-19 infections continue to reveal mental health targets, a process we must now be prepared to deal with.

Emerging Roles of Blood-Borne Intact and Respiring Mitochondria as Bidirectional Mediators of Pro- and Anti-Inflammatory Processes.

Over the past two decades, a major goal of our research group has been elucidation of the functional roles of several key regulatory molecules in proinflammatory preconditioning involved in the pathophysiology of seemingly diverse human disease states. By necessity, operational definitions of proinflammation must be intrinsically fluid based on recent advances in our understanding of complex regulation of innate and adaptive immune processes. Similar to systemic acute stress, a physiological proinflammatory state appears to be a key autoregulatory mechanism for maintaining optimal immune surveillance against potentially infective microorganisms, viruses, and toxic xenobiotics. Perturbation of normative biochemical and molecular mosaics of ongoing proinflammatory tone, exemplified by altered expression of pro- and anti-inflammatory cytokines and their respective protein complexes, is hypothesized to be a common modality for initiation and full expression of various autoimmune diseases and comorbid syndromes evolving from metabolic and metastatic diseases. The newly reported presence of "free" (extracellular) mitochondria exponentially adds to our hypothesis that in conditions of acute stress, a new source of potential ATP producers may be recruited and present to deal with such an acute process. Furthermore, given this phenomenon, an early surveillance role and a dysfunctional chronic inflammation-prolonging component may also be surmised.

Dysregulation of Nitric Oxide Signaling in Microglia: Multiple Points of Functional Convergence in the Complex Pathophysiology of Alzheimer Disease.

Current critical thinking has displaced the elaborated beta amyloid theory as the underlying unitary mechanism of Alzheimer disease (AD) in favor of concerted, long-term disruption or dysregulation of broad-based physiological processes. We present a critical discussion in which a chronic state of systemic proinflammation sustained over the course of several decades and engendered by ongoing metabolic or autoimmune disease is predicted to promote severe disruptions of central neurological processes. Specifically, long-term functional rundown of microglial-mediated phagocytic activity in concert with aberrant expression and cellular deposition of beta amyloid and tau protein facilitates formation of senile plaques and neurofibrillary tangles. Within this functional context, we hypothesize that early initiation events in the pathophysiology of AD may operationally involve a convergence of dysregulated peripheral and central constitutive nitric oxide signaling pathways resulting from a chronic state of systemic proinflammation and leading to severely dysfunctional "hyperactivated" microglia.

Burnout Syndrome and Lifestyle Among Primary School Teachers: A Czech Representative Study.

BACKGROUND Burnout is a state of vital exhaustion that is manifested on physical, cognitive, and emotional levels. Teachers work in a field where they are exposed daily to high job-related stressors, which can result in job change, a higher rate of unhappiness, and even earlier retirement. This study explored the relationship between job stressors, lifestyle, and burnout. MATERIAL AND METHODS Descriptive statistics were used to explore the burnout levels, together with t tests to compare between men and women, and regression analysis was performed to explore the relationship between the rates of burnout and lifestyle. RESULTS The overall sample size was 2394 teachers from primary schools. While males had higher emotional burnout, females reported higher physical burnout rates. We found that higher income was associated with less burnout, and a healthier lifestyle is associated with lower burnout rates. Teachers who take time for family and personal interests have significantly lower rates of burnout than those that do not. CONCLUSIONS Based on our results, we propose that teachers should be informed about the risk of burnout. We found that some teachers reported they do not know what burnout syndrome is. The primary aim should be to increase awareness. In fact, burnout is a major threat to those who are perfectionists and who tend to work overtime.

Sexual Dysfunctions in Obese Women Before and After Bariatric Surgery.

BACKGROUND Obesity and associated comorbidities increase the probability of sexual disorders. The present study evaluated sexual satisfaction levels in obese women prior to and following bariatric surgery, utilizing the validated Female Sexual Function Index (FSFI) to also evaluate the sexual satisfaction in obese and non-obese women. MATERIAL AND METHODS 60 obese women (mean initial BMI of 43.7±5.9 kg/m²; mean age of 41.7±10.8 years) were administered the questionnaire on sexual function (FSFI) preceding bariatric surgery (laparoscopic adjustable gastric banding, 22 women; gastric plication, 33 women; and biliopancreatic diversion, 5 women), 6 months and 12 months after the procedure, i.e., following substantial weight reduction (final mean BMI of 35.5±5.5 kg/m²). The control group comprised 60 non-obese women (mean BMI of 22.2±1.9kg/m²; mean age of 36.4±10.7 years). RESULTS Our findings indicate that baseline sexual function in the preoperative obese females was significantly lower than in non-obese women, with p<0.01 in each domain. Data gathered at the 6- and 12-month points following the procedure indicated no significant difference. Before the procedure, 31 obese subjects (51.6%) exceeded the cutoff for FSD, at the 6-month evaluation point, 17 women (39.5%) exceeded the cutoff, and at 12 months postoperatively, 18 subjects (41.9%) exceeded the cutoff, indicative of FSD. Among the non-obese controls, only 9 subjects (15%) exceeded the cutoff threshold. CONCLUSIONS These findings show that substantive weight reduction resulting from bariatric surgery results in reduced sexual dysfunction in female subjects.

Clinical Implications of the Perception of Time in Attention Deficit Hyperactivity Disorder (ADHD): A Review.

Attention deficit hyperactivity disorder (ADHD) is a lifelong neurodevelopmental disorder that can affect many areas of the daily life of individuals and is associated with poor health outcomes and with debilitating deficits in executive function. Recently, increasing numbers of research studies have begun to investigate the associations between neural and behavioral manifestations of ADHD. This review summarizes recent research on the perception of time in ADHD and proposes that this symptom is a possible diagnostic characteristic. Controlled studies on time perception have compared individuals with ADHD with typically developing controls (TDCs) and have used methods that include the Zimbardo Time Perspective Inventory (ZTPI). Practical approaches to time perception and its evaluation have shown that individuals with ADHD have difficulties in time estimation and discrimination activities as well as having the feeling that time is passing by without them being able to complete tasks accurately and well. Although ADHD has been associated with neurologic abnormalities in the mesolimbic and dopaminergic systems, recent studies have found that when individuals with ADHD are treated medically, their perception of time tends to normalize. The relationship between ADHD and the perception of time requires greater attention. Further studies on time perception in ADHD with other abnormalities, including executive function, might be approaches that refine the classification and diagnosis of ADHD and should include studies on its varied presentation in different age groups.

Decreased Central Nervous System Grey Matter Volume (GMV) in Smokers Affects Cognitive Abilities: A Systematic Review.

Although cigarette smoking is a leading cause of preventable mortality, tobacco is consumed by approximately 22% of the adult population worldwide. Smoking is also a risk factor for cardiovascular disease, affects brain processing, and is a recognized risk factor for Alzheimer disease (AD). Tobacco toxins (e.g., nicotine at high levels) inhaled in smoke may cause disorders resulting in preclinical brain changes. Researchers suggest that there are differences in brain volume between smokers and non-smokers. This review examines these differences in brain grey matter volume (GMV). In March/April 2015, MedLine, Embase, and PsycINFO were searched using the terms: "grey matter" AND "voxel-based" AND "smoking" AND "cigarette". The 4 studies analyzed found brain GMV decreases in smokers compared to non-smokers. Furthermore, sex-specific differences were found; while the thalamus and cerebellum were affected in both sexes, decreased GMV in the olfactory gyrus was found only in male smokers. Age-group differences were also found, and these may suggest pre-existing abnormalities that lead to nicotine dependence in younger individuals. Only 1 study found a positive correlation between number of pack-years smoked and GMV. Smoking decreases GMV in most brain areas. This decrease may be responsible for the cognitive impairment and difficulties with emotional regulation found in smokers compared with non-smokers.

Reciprocal Evolution of Opiate Science from Medical and Cultural Perspectives.

Over the course of human history, it has been common to use plants for medicinal purposes, such as for providing relief from particular maladies and self-medication. Opium represents one longstanding remedy that has been used to address a range of medical conditions, alleviating discomfort often in ways that have proven pleasurable. Opium is a combination of compounds obtained from the mature fruit of opium poppy, papaver somniferum. Morphine and its biosynthetic precursors thebaine and codeine constitute the main bioactive opiate alkaloids contained in opium. Opium usage in ancient cultures is well documented, as is its major extract morphine. The presence of endogenous opiate alkaloids and opioid peptides in animals owe their discovery to their consistent actions at particular concentrations via stereo select receptors. In vitro expression of morphine within a microbiological industrial setting underscores the role it plays as a multi-purpose pharmacological agent, as well as reinforcing why it can also lead to long-term social dependence. Furthermore, it clearly establishes a reciprocal effect of human intelligence on modifying evolutionary processes in papaver somniferum and related plant species.

Microbiome: A Potential Component in the Origin of Mental Disorders.

It is not surprising to find microbiome abnormalities present in psychiatric disorders such as depressive disorders, bipolar disorders, etc. Evolutionary pressure may provide an existential advantage to the host eukaryotic cells in that it survives in an extracellular environment containing non-self cells (e.g., bacteria). This phenomenon is both positive and negative, as with other intercellular processes. In this specific case, the phenomenal amount of information gained from combined bacterial genome could enhance communication between self and non-self cells. This can be coupled to both pathological processes and healthy ones. In this review, we chose to examine potential associated disorders that may be coupled to the microbiome, from the perspective of their bidirectional communication with eukaryotic cells in the gut. Cognition, being the newest neural networking functionality to evolve, consumes a good amount of organismic energy, 30% of which arises from the gut flora. Furthermore, the mammalian gut is highly innervated and has a highly developed immune component, reflecting brain complexity. The brain-gut axis uses similar molecular messengers as the brain, which affects bacterial processes as well. Thus, any modification of normal bacterial processes may manifest itself in altered behavior/cognition, originating from the gut. The origin of some disorders associated with this bidirectional communication may be harnessed to restore normal functioning.

[Work-related stress and mental health - can work lead to mental disorders?] / Pracovní stres a dusevní zdraví - muze práce vést k dusevním poruchám?

In the past two decades, special attention was paid to mental health issues. The available literature suggests, for example, the relationship between the workload and mental discomfort and the occurrence of myocardial infarction. This article focuses mainly on the issue of work-related stress and its impact on mental health. In this context, it must be acknowledged that possible psychological problems due to work are not only employees problem. These difficulties can significantly affect performance - and thus they should be the concern of the employer, but also of customers, clients and patients who come into contact with the worker who might develop some mental problems, due to the nature of his work and working conditions. This article provides an overview of the various factors affecting the mental health of employees. These are, for example, work demands, working hours and workplace relations. In conclusion, it brings results of Czech study examining job stress among working population.

[With children against obesity]. / S detmi proti obezite.

The project "With Children Against Obesity" (www.sdetmiprotiobezite.cz) is an original and innovative prevention website, which is currently unparalleled in the Czech Republic. It is a rare project that deals not only with the issue of childhood obesity for the general public but also for professionals. The website offers a comprehensive view of the prevention and treatment of overweight and obese children. The project offers original products that can be used in the everyday clinical practice for specific individuals with risks of developing obesity, including their family background. It follows the basic principles of prevention of metabolic diseases.