Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.

Circadian rhythm disruption is increasingly considered an environmental risk factor for the development and exacerbation of inflammatory bowel disease. We have reported in a previous study that nychthemeral dysregulation is associated with an increase in intestinal barrier permeability and inflammation in mice with dextran sulfate sodium (DSS)-induced colitis. To investigate the effect of circadian rhythm disruption on the composition and diversity of the gut microbiota (GM). Sixty male C57BL/6J mice were divided initially to two groups, the shifted group (n=30) exposed to circadian shifts for three months and the non-shifted group (n=30) under a normal light-dark cycle. The mice of the shifted group were cyclically housed for five days under the normal 12:12 hour light-dark cycle followed by another five days under reversed light-dark cycle. At the end of the three months a colitis was induced by 2 % DSS given in the drinking water of 30 mice. Animals were then divided into four groups (n=15 per group), sham group non-shifted (Sham-NS), sham group shifted (Sham-S) and DSS non-shifted (DSS-NS) and DSS shifted (DSS-S). Fecal samples were collected from rectal content to investigate changes in GM composition by DNA extraction followed by high-throughput sequencing of the bacterial 16S rRNA gene. The mouse GM was dominated by three phyla: Firmicutes, Bacteroidetes and Actinobacteria. The Firmicutes/Bacteroidetes ratio decreased in mice with induced colitis. The richness and diversity of the GM were reduced in the colitis group, especially in the group with inverted circadian rhythm. Moreover, GM composition was also modified in the inverted circadian rhythm group, with an increase in Alloprevotella, Turicibacter, Bacteroides and Streptococcus genera. Circadian rhythm inversion exacerbates GM dysbiosis to a less rich and diversified extent in a DSS-induced colitis model. These findings shows a possible interplay between circadian rhythm disruption, GM dynamics, and colitis pathogenesis.

Huntington’s disease (HD) causes progressive movement disorders and cognitive deficits. Besides, sleep disturbances and emotional distress are prominent clinical signatures of HD. The experimental subjects and HD human brains display altered regenerative plasticity resulting from aberrant neurogenic and nonneurogenic areas. Sleep disorders, emotional disruption, and cognitive deficits have been linked to impaired cell cycle events of neural stem cells (NSC) in neurodegenerative disorders. In a physiological state, circadian clock gene pathways play important roles in the regulation of the proliferation and differentiation of NSC, whereas the irregular circadian clock pathway is attributed to impairment in the neurogenic process. The recent advancement of chemogenetic-based approaches represents a potential scientific tool to rectify the abnormal circadian clock which may aid in mitigating neurogenic failure in the brain. Notably, GABAergic vasoactive intestinal peptide (VIP)-expressing neurons in the brain plays a key role in the regulation of neuroplasticity and circadian rhythm. Thus, this conceptual review article addresses the potential link between sleep disorder and aberrant neurogenic events in HD and proposes chemogenetic kindling of vasoactive intestinal peptide (VIP) -expressing GABAergic neurons in the brain as a therapeutic strategy for reprogramming the clock gene pathways in mitigating the neurodegenerative failure in HD.

We investigated if the abnormal sleep-wake rhythms in infants are related to the future development of autism spectrum disorder (ASD), using questionnaire from September to October 2016. The parents of a total 160 children with ASD (male, n=123; female, n=37) recruited from the two hospitals in K and H cities and as a control group, 145 children (male, n=75; female, n=70) recruited from four nursery schools in T city. Fisher’s exact test was used for the comparison of categorical variables. The associations of bedtime and waking time on weekdays and holidays in infancy, at 1-3≦ (1-3) years of age and at 3-5 ≦ (3-5)years of age with the prevalence of ASD were analyzed using a multivariable logistic regression analysis. Especially by 3 years of age, the following factors were associated with an increased risk of developing ASD in the future: 1) short sleep (<8h), 2) long time to fall asleep (>60min), 3) sleep onset time after 22:00h, 4) wake-up time after 07:00h and/or 08:00h on weekdays and holidays, respectively, 5) frequent (>3 times) and long-term awakening (>60min). Misalignment and/or shift of the sleep-wake circadian rhythm in infant may be one of the precursors and/or risk factor to the future development of ASD.

Patients with degenerative diseases refer to feeling more pain during the night. However, it is unknown whether spinal nociception can be circadian and how is it controlled. We investigated whether the paw withdrawal threshold (PWT) could exhibit physiological circadian behavior as well as the contribution of the dopaminergic A11 nucleus and the spinal dopamine (DA) receptors (DRs) on the circadian PWT and the spinal clock gene transcription. Results revealed that control rats present a circadian PWT. Injecting 6-hydroxidopamine (6-OHDA) into the dopaminergic A11 nucleus reduced DA tissue content in the lumbar spinal cord, abolished the circadian PWT, induced allodynia, and reduced Period 1 and 2 (Per1 and 2), retinoid-related orphan receptor α (Rorα), Cryptochrome 1 (Cry1), and brain and muscle aryl-hydrocarbon receptor nuclear translocator-like protein (Bmal) mRNA. Likewise, administration of D1-like and D2-like DR antagonists blunted circadian PWT, producing allodynia, and altered the clock genes mRNA. In contrast, administration of D1-like or D2-like DR agonists blocked 6-OHDA-induced allodynia. This study shows that the spinal cord has physiological circadian PWT, which is modulated by the descending dopaminergic A11 through differential activation of the spinal DRs. Also, A11 nuclei and spinal DRs can regulate the clock gene transcription, which can likely modulate the circadian PWT.

Human Activity Recognition (HAR) technology enables continuous behavior monitoring, particularly valuable in healthcare. This study investigates the viability of using an ear-worn motion sensor for classifying daily activities, including lying, sitting/standing, walking, ascending stairs, descending stairs, and running. Fifty healthy participants (between 20 and 47 years old) engaged in these activities while under monitoring. Various machine learning algorithms, ranging from interpretable shallow models to state-of-the-art deep learning approaches designed for HAR, were employed for classification. Results demonstrate the ear sensor's efficacy, with deep learning models achieving 98% accuracy rate of classification. The obtained classification models are agnostic regarding which ear the sensor is worn and robust against moderate variations in sensor orientation (e.g., due to differences in auricle anatomy), meaning no initial calibration of the sensor orientation is required. The study underscores the ear's efficacy as a suitable site for monitoring human daily activity and suggests its potential for combining HAR with in-ear vital signs monitoring. This approach offers a practical method for comprehensive health monitoring by integrating sensors in a single anatomical location. This integration facilitates individualized health assessments, with potential applications in tele-monitoring, personalized health insights, and optimizing athletic training regimes.

Fragile X syndrome (FXS) is caused by the full mutation in the FMR1 gene on the Xq27.3 chromosome region. It is the most common monogenic cause of Autism Spectrum Disorder (ASD) and inherited intellectual disability (ID). Besides ASD, ID and other issues, individuals with FXS may exhibit sleep problems and impairment of circadian rhythm (CR). The Drosophila melanogaster models of FXS, such as dFMR1B55, present excellent model for research in the FXS field. During this study, sleep pattern and CR in dFMR1B55 mutants were analyzed, using a new platform based on continuous high-resolution videography in integration with a highly-customized version of software. This methodology provides more sensitive results, which could be crucial for all further research in this model of fruit flies. The study revealed that dFMR1 B55 male mutants can be considered weak rhythmic flies rather than totally arrhythmic, and present a good alternative animal model of genetic disorder, which includes impairment of CR and sleep behavior. The combination of videography and software used in the current study should be recommended as a gold-standard methodology for such further research.

(1) Background: The aim of this study was to investigate the circadian rhythms of tongue features according to the effects of physiological phases over a 24-hour period. (2) Methods: Fifteen healthy participants aged 20 to 69 years were recruited. The participants did not have current chronic diseases or past diseases and had to meet the inclusion and exclusion criteria. The participants stayed at the Gil Hospital for a duration of 2 nights and 3 days. On the first day, at 18:00, they consumed their allocated portions of food and water and then completed a questionnaire. At approximately 21:00, their tongue images were acquired using a computerized tongue image acquisition system, following which they slept for 8 hours, commencing at 23:00. Measurements were taken from 07:00 through 21:00 on the second day, and the final acquisition was taken at 07:00 on the following morning, resulting in a total of eight images. The circadian rhythm was authenticated and quantified utilizing the single cosinor analysis, a technique for periodic regression analysis for fitting a 24-hour cosine curve. (3) Results: Cosinor analysis revealed that all tongue features were significantly related to circadian rhythm. (4) Conclusions: The results of this study may be important for considering the time of day at which the tongue is observed and tongue status is evaluated.

The reasons for the circular sense of human color perception generated by two sorts of color opponent neurons and three cone types are not well understood. Here we use geometrical analysis to examine the hypothesis that opponency, the recursive nature of color perception, and trichromacy arise as the most efficient ways of distinguishing spectrally different points on a plane using a minimum of color classes and receptor types.

(1) Background: Sudden Infant Death Syndrome (SIDS) represents unexplained and sudden deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for prolonged QTc or Long QT Syndrome (LQTS) should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiogram (ECG) could identify congenital heart defects (CHD) early, especially those not detected at birth. Infants with prolonged QT intervals typically undergo genetic analysis for Long QT Syndrome; (2) Methods: The study involved infants aged 20-40 days, born clinically healthy, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHD identified immediately after birth, as well as those who underwent ECG or echocardiogram for other clinical or historical indications, were excluded from the study. The data were analyzed using SPSS version 22.0; (3) Results: Of the 42,200 infants involved, 2,245 were enrolled, with 39.9% being males. Subsequently, 164 children (37.8% males) with prolonged QT intervals underwent further diagnostic investigations. Genetic mutations were identified in 11 out of 18 tested children. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Medications used included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%; (4) Conclusions: The screening has proven effective in early diagnosing Long QT Syndrome and other cardiac rhythm anomalies, with additional benefits in detecting mutations and/or QTc prolongations in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening.

Achieving synchronization between the central and peripheral body clocks is essential for ensuring optimal metabolic function. Meal timing is an emerging field of research that investigates the influence of eating patterns on our circadian rhythm, metabolism, and overall health. This narrative review examines the relationship between meal timing, circadian rhythm, clock genes, circadian hormones, and metabolic function. It analyzes existing literature and experimental data to explore the connection between mealtime, circadian rhythms, and metabolic processes. The available evidence highlights the importance of aligning mealtime with the body’s natural rhythms to promote metabolic health and prevent metabolic disorders. Specifically, studies show that consuming meals later in the day is associated with a elevated prevalence of metabolic disorders, while early time-restricted eating, such as having an early breakfast and an earlier dinner, improves levels of glucose in the blood and substrate oxidation. Circadian hormones, including cortisol and melatonin, interact with mealtimes and play vital roles in regulating metabolic processes. Cortisol, aligned with dawn in diurnal mammals, activates energy reserves, stimulates appetite, influences clock gene expression, and synchronizes peripheral clocks. Consuming meals during periods of elevated melatonin levels, specifically during the circadian night, has been correlated with potential implications for glucose tolerance. Understanding the mechanisms of central and peripheral clock synchronization, including genetics, interactions with chronotype, sleep duration, and hormonal changes, provides valuable insights for optimizing dietary strategies and timing. This knowledge contributes to improved overall health and well-being by aligning mealtime with the body’s natural circadian rhythm.

Chronic joint inflammatory disorders such as osteoarthritis and rheumatoid arthritis have in common an upsurge of inflammation, and oxidative stress, resulting in progressive histological alterations and disabling symptoms. Currently used conventional medication (ranging from pain-killers to biological agents) is potent, but frequently associated with serious, even life-threatening side effects. Used for millennia in traditional herbalism, medicinal plants are a promising alternative, with lower rate of adverse events and an efficiency frequently comparable with that of conventional drugs. Nevertheless, their mechanism of action is in many cases elusive and/or uncertain. Even many of them have been proved effective in studies done in vitro or on animal models, there is a scarcity of human clinical evidence. The purpose of this review is to summarise the available scientific information on these joint-friendly medicinal plants, which have been already tested in human studies: Arnica montana, Boswelliaspp., Curcuma spp., Equisetum arvense, Harpagophytumprocumbens, Salix spp., Sesamumindicum, Symphytumofficinalis, Zingiberofficinalis, Panaxnotoginseng, Whitaniasomnifera.

This review summarizes current understanding of the interaction between circadian rhythms of gene expression and epigenetic clocks characterized by the specific profile of DNA methylation in CpG-islands which mirror the chronological age of individual cells and the entire organism. Basic mechanisms of regulation for circadian genes CLOCK- BMAL1 as well as downstream clock-controlled genes (ССG) are also discussed here. It has been shown that circadian rhythms operate by finely tuned regulation of transcription and rely on various epigenetic mechanisms including activation of enhancers / suppressors, acetylation / deacetylation of histones and other proteins as well as DNA methylation. Overall, up to 20% of all genes expressed by the cell are subject to expression oscillations associated with circadian rhythms. Also included in the review is a brief list of genes involved in the regulation of circadian rhythms, along with genes important for metabolic control, aging, and oncogenesis. Knocking out some of them (for example, Sirt1) accelerates the aging process, while overexpression of Sirt1, on the contrary, protects against age-related changes. Circadian regulators control a number of genes that activate the cell cycle (Wee1, c-Myc, p20, p21, and Cyclin D1) and regulate histone modification and DNA methylation. Approaches for determining the epigenetic age from methylation profiles across CpG islands in individual cells are described. DNA methylation, which characterizes the function of the epigenetic clock, appears to link together such key biological processes as regeneration and functioning of stem cells, aging and malignant transformation. Finally, main features of adult stem cell aging in stem cell niches and current possibilities for modulating the epigenetic clock as part of antiaging therapy are discussed.

Drosophila circadian circuit is one of the best described neural circuits but is complex enough to obscure our understanding of how it actually works. Animals’ rhythmic behavior, the seemingly simple outcome of their internal clocks, relies on the interaction of heterogeneous clock neurons that are spread across the brain. Direct observations of their coordinated network interactions can bring us forward in understanding the circuit. The current challenge is to observe activity of each of these neurons over a long span of time –hours to days– in live animals. Here we review the progress in circadian circuit interrogation powered by in vivo calcium imaging.

This review aims to explore the intricate relationship between epigenetic mechanisms, stress, and affective disorders, focusing on how early life experiences and coping mechanisms contribute to susceptibility to mood disorders. Epigenetic factors play a crucial role in regulating gene expression without altering the DNA (deoxyribonucleic acid) sequence, and recent research has revealed associations between epigenetic changes and maladaptive responses to stress or psychiatric disorders. A scoping review of 33 studies employing the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses – Statement) guidelines investigates the role of stress-induced epigenetic mechanisms and coping strategies in affective disorders' occurrence, development, and progression. The analysis encompasses various stress factors, including childhood trauma, work-related stress, and dietary deficiencies, alongside epigenetic changes such as DNA methylation and altered gene expression. Findings indicate that specific stress-related genes frequently exhibit epigenetic changes associated with affective disorders. Moreover, the review examines coping mechanisms in patients with bipolar disorder and major depressive disorder, revealing mixed associations between coping strategies and symptom severity. While active coping is correlated with better outcomes, emotion-focused coping may exacerbate depressive or manic episodes. Overall, this review underscores the complex interplay between genetic predisposition, environmental stressors, coping mechanisms, and affective disorders. Understanding these interactions is essential for developing targeted interventions and personalized treatment strategies for individuals with mood disorders. However, further research is needed to elucidate specific genomic loci involved in affective disorders and the clinical implications of coping strategies in therapeutic settings.

The spectrum, intensity and overlap of symptoms between FGIDs and other gastrointestinal disorders characterize patients with FIGDs, who are incredibly different in their backgrounds. An additional challenge with regard to the diagnosis and treatment's applicability is the ongoing expansion of the risk factors believed to be connected to these disorders. Many cytokines and inflammatory cells have been found causing the continuous existence of low-inflammation, which is thought to be a basic pathophysiological process. The idea of the gut-brain axis has been created to offer a basic framework for the complex interactions that occur between the nervous system and intestinal functions, including the involvement of the gut bacteria. In this review paper, we intend to promote a hypothesis that FGIDs, should be seen through the perspective of the network of the neuroendocrine, immunological, metabolic and microbiome pathways. Hypothesis arises from an increased understanding of chronic inflammation as a systemic disorder, being omnipresent in chronic health conditions. Better understanding of inflammation role in the pathogenesis of FGIDs can be achieved by clustering markers of inflammation with data indicating symptoms, comorbidities, and psycho-social factors. Finding subclasses among related entities of FGIDs, may reduce patient heterogeneity and help clarify pathophysiology for better treatment.

Depressive disorder in childhood and adolescence is a highly prevalent mood disorder that tends to recur throughout life. Untreated mood disorders can adversely impact a patient's quality of life and cause socioeconomic loss. Thus, an accurate diagnosis and appropriate treatment is crucial. However, until now, diagnoses and treatments are conducted according to clinical symptoms. Objective and biological validation are lacking. This may result in a poor outcome for patients with depressive disorder. Research has been conducted to identify the biomarkers that are related to depressive disorder. Cumulative evidence has revealed that certain immunologic biomarkers in-cluding brain-derived neurotrophic factor (BDNF) and cytokines, gastrointestinal biomarkers, hormones, oxidative stress, and certain hypothalamus-pituitary axis biomarkers are associated with depressive disorder. This article reviews the biomarkers related to the diagnosis and treatment of pediatric depressive disorders. To date, clinical biomarker tests are not yet available for diagnosis or for the prediction of treatment prognosis. However, cytokines such as Interleukin-2, interfer-on-gamma, tumor necrosis factor-alpha, and BDNF have shown significant results in previous studies of pediatric depressive disorder. These biomarkers have the potential to be used for diagnosis, prognostic assessment, and group screening for those at high risk.

Neuronal PAS domain protein 2 (NPAS2) is a hemeprotein comprising a basic helix-loop-helix domain (bHLH) and two heme-binding sites, the PAS-A and PAS-B domains. This protein acts as a pyridine nucleotide-dependent and gas-responsive CO-dependent transcription factor and is encoded by a gene whose expression fluctuates with circadian rhythmicity. NPAS2 can heterodimerize with ARNTL in the activating limb of the transcriptional/translational feedback loop operating the circadian clock circuitry. NPAS2 can functionally substitute for the core transcription factor and histone/protein acetylase CLOCK in the molecular clockwork endowing central oscillators in the suprachiasmatic nuclei of hypothalamus as well as in peripheral oscillators in the cell of other body tissues, such as the liver and kidney.

Objectives: The study aimed to develop a deep learning-based edge AI model deployed on electrocardiograph (ECG) devices for real-time detection of atrial fibrillation (AF)-risk during sinus rhythm (SR) using standard 10-second 12-lead electrocardiograms (ECGs). Methods: A novel approach was used to convert standard 12-lead ECGs into binary images for model input, and a lightweight convolutional neural network (CNN)-based model was trained using data collected by the Japan Agency for Medical and Research Development (AMED) between 2019 and 2022. Patients over 40 years old with digital, SR ECGs were retrospectively enrolled and divided into AF and non-AF groups. Data labeling was supervised by cardiologists. The dataset was randomly allocated into training, validation, and internal testing datasets. External testing was conducted on data collected from other hospitals.　Results: The best-trained model achieved an AUC of 0.82 and 0.80, sensitivity of 79.5% and 72.3%, specificity of 77.8% and 77.7%, precision of 78.2% and 76.4%, and overall accuracy of 78.6% and 75.0% in the internal and external testing datasets, respectively. The deployed model and app package utilized 2.5MB and 40MB of the available ROM and RAM capacity on the edge ECG device, correspondingly. Processing time for AF-risk detection was approximately 2 seconds.　Conclusion: The model maintains comparable performance and improves its suitability for deployment on resource-constrained ECG devices, thereby expanding its potential impact to a wide range of healthcare settings. Its successful deployment enables real-time AF-risk detection during SR, allowing for timely intervention to prevent AF-related serious consequences like stroke and premature death.

The ubiquitous peptide endothelin is currently under investigation as a modulatory factor of autonomic responses to acute emotional stress. Baseline plasma levels of endothelin alter blood pressor responses, but it remains unclear whether autonomic activity and arrhythmogenesis are affected. We recorded sympathetic and vagal indices (derived from heart rate variability analysis), rhythm disturbances, voluntary motion, and blood pressure after acute emotional stress in conscious rats with implanted telemetry devices. Two strains were compared, namely wild-type and ETB-deficient rats, the latter displaying elevated plasma endothelin. No differences in heart rate or blood pressure were evident, but sympathetic responses were blunted in ETB-deficient rats, contrasting prompt activation in wild-type rats. Vagal withdrawal was observed in both strains at the onset of stress, but vagal activity was subsequently restored in ETB-deficient rats, accompanied by low voluntary motion during recovery. Reflecting such distinct autonomic patterns, frequent premature ventricular contractions were recorded in wild-type rats, as opposed to sinus pauses in ETB-deficient rats. Thus, chronically elevated plasma endothelin levels blunt autonomic responses to acute emotional stress, resulting in vagal dominance and bradyarrhythmias. Our findings provide further insights into the pathophysiology of stress-induced tachyarrhythmias and syncope.

The circadian clock regulates daily changes in behavioral, endocrine and metabolic activities in mammals. Circadian rhythms in cellular physiology are significantly affected by aging. In particular, we previously found that aging has profound impact on daily rhythms in mitochondrial functions, leading to increased oxidative stress. However, this is unlikely due to malfunction of molecular clocks in the suprachiasmatic nucleus or peripheral tissues, as robust clock oscillations are observed therein in old animals. Nonetheless, aging induces changes in gene expression levels and rhythms in various peripheral and probably central tissues. In this article, we review findings on the roles of the circadian clock and aging in regulating mitochondrial rhythms and redox homeostasis. Chronic sterile inflammation is implicated in mitochondrial dysfunction and increased oxidative stress during aging. In particular, upregulation of CD38 by inflammatory response can disturb mitochondrial functions in multiple ways.

In patients with schizophrenia, metabolic syndrome is associated with cognitive impairments. We carried out a second analysis of data from a longitudinal trial to examine the relationship between weight gain and cognitive function in patients with first-episode schizophrenia (FES) over the first 6-month antipsychotic treatment. Baseline and 6-month endpoint measurements were taken for both cognitive function and body weight. Linear and logistic regression analyses were applied to investigate the bidirectional relationship between weight gain and cognitive function. Clinically relevant weight gain (CRW) was defined as an increase in body weight ex-ceeding 7%. The final analysis included 337 participants. Lower baseline scores in processing speed (OR=0.837, p=0.007), working memory and attention (OR=0.889, p=0.043), and executive function (OR=0.863, p=0.006) domains were significantly associated with CRW at the 6-month endpoint. After adjusting for confounders, CRW was found to be associated with improvement in the Brief Visuospatial Memory Test (p=0.036). The findings suggest that patients with lower baseline cognitive performance experienced more substantial weight gain. Conversely, weight gain was correlated with cognitive improvements, particularly in the domain of visual learning and memory. This suggested a potential bidirectional relationship between weight gain and cog-nitive function in patients with first-episode schizophrenia.

The growing awareness of the biological effects of artificial light on humans has stimulated ample research. It is now widely accepted that asynchrony between artificialand natural light-dark cycles can elicit severe detrimental health effects. New research has been devoted to lighting solutions that dynamically change their color to mimic spectral changes of daylight and to account for human needs. However, in some situations, the visual properties of light must be preserved: For example professional TV video editors and shift workers who must work under standardized lighting conditions to do color correction in post-production. We have investigated the possibility to tune circadian effects using white lights that are spectrally different but nonetheless have similar color coordinates thus appear as a similar white tone. Our simulation results indicate that it is possible to modulate circadian light effects by combining LEDs for neutral white (4000 K), a widely used white tone for indoor lighting in europe. The results also show that the solutions combining single-color LEDs do however not meet the quality criteria from the visual point of view because their color rendering ability decays to unacceptable low levels. Combining narrowband LEDs with a broadband white LED improves the color rendering quality and we show how far circadian light effects can be tuned according to common theoretical models. The aim is to reflect daylight situations with artificial lighting, thus having a high melatonin suppression in the morning and low melatonin suppression in the evening. As a consequence our aim is to show what maximum and minimum circadian effect is possible with the same set of LEDs.

Improper sitting positions are known as the primary reason for back pain and the emergence of musculoskeletal disorders (MSD) among individuals who spend prolonged time working with computer screens, keyboards, and mice. At the same time, it is well understood that automated technological tools can play an important role in the process of unhealthy habit alteration, so plenty of research efforts are focused on research and technology development (RTD) activities that aim to provide support to the prevention of back pain or the development of MSD. Here, we report on creating a new resource in support of RTD activities aiming at the automated detection of improper sitting positions. It consists of multimodal multisensory recordings of 100 persons made with a video recorder, camera, and wrist-attached sensors that capture physiological signals (PPG, EDA, Skin temperature), as well as motion sensors (three-axis accelerometer). Our multimodal multisensory dataset (MMD-MSD) opens new opportunities for modeling the body stance (sitting posture and movements), physiological state (stress level, attention, emotional arousal, valence), and performance (success rate on the Stroop test) of people working with a computer. Finally, we demonstrate two use cases: improper neck posture detection from pictures and cognitive load detection from physiological signals.

This communication explores the transition from Cognitive Behavioural Therapy (CBT) to a more holistic model, named Complex Therapy, developed by Tullio Scrimali for explaining and treating mental disorders. The Author delves into the limitations of traditional CBT and introduces an innovative framework that integrates multiple therapeutic modalities. While CBT is based on the study and modification of behaviour and cognition, Complex Therapy includes, in its focus, the theory of human relationships, the attachment theory, neuroscience, applied neuroscience, complex systems theory and ecology.Complex Therapy addresses the multifaceted nature of mental health issues by combining evidence-based techniques with personalized care strategies. The goal is to enhance patient outcomes through a tailored, comprehensive treatment plan that adapts to the evolving needs of individuals facing mental health challenges.Two innovative and original items which Scrimali has developed, which are a device for Applied Neuroscience MindLAB Set and a new botanical drug, NegEnt, are presented and discussed.The topic also describes, an original and integrated protocol, named Negative Entropy, the author has developed for treating a challenging disorder, such as schizophrenia, he renamed Entropy of Mind.

The western flower thrips, Frankliniella occidentalis, is invasive and polyphagous. Its visual signal plays a crucial role in host location, suggesting that thrips has diurnal behavior. However, any diel rhythmicity of the thrips behavior is not yet well understood. This study analyzed the diurnal rhythmicity of the feeding and mating behaviors of thrips, and the patterns were explained in terms of diel rhythmicity by assessing the expression of genes associated with the circadian clock. Most feeding behaviors were observed during photophase in both larvae and adults. In mating behavior, which is mainly exhibited in 2~3 days-old young adults after emergence, most adults copulated at photophase. This diurnal pattern of the mating behavior was further supported by the analysis of a temporal calling behavior for mating, which was biased toward photophase. Four genes associated with the circadian clock were predicted in the F. occidentalis genome: period (PER), Timeless (TIM), Doubletime (DBT), and clock (CLK). All these genes exhibited a characteristic diel pattern in their gene expressions in a 24 h-period. The high expression peaks of these genes except for DBT were observed at photophase. To confirm the functional association of these genes with the feeding and mating behaviors, individual RNA interference specific to each gene was executed by feeding the gene-specific double-stranded RNA. Aside from DBT, suppression of these gene expressions resulted in significant deviations of the diel rhythms of the behaviors. These results suggest that the genetic components of the diel rhythmicity mediate the diurnal feeding and mating behaviors of F. occidentalis.

Abstract: The emergence of the COVID-19 pandemic has led to the rapid and worldwide devel-opment and investigation of multiple vaccines. While most side effects of these vaccines are mild and transient, potentially severe adverse events may occur and involve the endocrine system. This narrative review aims to explore the current knowledge on potential endocrine adverse effects following COVID-19 vaccination, with thyroid disorders being the most common. Data about pi-tuitary, adrenal, diabetes, and gonadal events will also be reviewed. This review also provides a comprehensive understanding of the pathogenesis of endocrine disorders associated with SARS-CoV-2 vaccines. A PubMed/MEDLINE, Embase database (Elsevier), and Google Scholar research were performed. Case reports case series, original studies, and reviews written in English and published online up to 31 August 2023 were selected and reviewed. Data on endocrine adverse events of SARS-CoV-2 vaccines is accumulating. However, their causal relationship with COVID-19 vaccines is not strong enough to make a definite conclusion, and further studies are needed to clarify the pathogenesis mechanisms of endocrine disorders linked to COVID-19 vac-cines.

Chronobiotics is a group of drugs utilized to modify circadian rhythms targeting clock-associated molecular mechanisms. The circadian clock is known as a controller of numerous processes standing behind aging. Hypothesis: KL001 and KS15 targeting CRY, affect lifespan, locomotor activity and circadian rhythm of Drosophila melanogaster. We observed a slight (2%, p<0.001) geroprotective effect on median lifespan (5 µM solution of KL001 in 0.1% DMSO) and a 14% increase in maximum lifespan in the same group. KS15 10 µM solution extended males’ median lifespan by 8% (p <0.05). The statistically significant positive effects of KL001 and KS15 on lifespan were not observed in female flies. KL001 5 µM solution improved locomotor activity in young male imagos (p<0.05) and elevated morning activity peak in aged imagos and modified robustness of circadian rhythms, leaving the period intact. KS15 10 µM solution decreased the locomotor activity in constant darkness and minimized the number of rhythmic flies. KL001 5 µM solution improved by 9% the mean starvation resistance in male flies (p<0.01), while median resistance was elevated by 50% (p<0.0001). This phenomenon may suggest the presence of the mechanism associated with improvement of fat body glucose depos’ utilization in starvation conditions which is activated by dCRY binding KL001.

The circadian clock is a 24-hour cycle within the body that regulates various factors, including sleep, body temperature, and hormone secretion. It allows the body to adjust to the light and dark cycle. Disruptions to the circadian rhythm are important risk factors for many diseases, including neurodegenerative illnesses. The central clock is controlled by the clock genes in the suprachiasmatic nucleus (SCN) of the brain, and one of the main functions of the circadian clock is to regulate lipid metabolism. There has been a lack of investigation on the circadian regulation of lipid metabolism-related apolipoprotein genes in the brain; thus, this study sought to summarize the rhythmic expression of clock genes and lipid metabolism-related apolipoprotein genes within the SCN of Mus musculus. Out of the 20 apolipoprotein genes that were studied by the published database, all 9 genes were highly expressed in the SCN. Most of the 6 genes showed rhythmic expression in the brain of mice, suggesting that the master clock might regulate them. The results, therefore, reveal a potential target for preventing and treating circadian disorders. We summarized most studies of lipid-related apolipoprotein genes within limited locations of the SCN and brain to further understand how disordered cerebral lipid metabolism causes multiple brain diseases and disorders. We reviewed recent studies, determined the unexplored questions, and identified a potential direction for further research.

We present a summary of our protocol for employment of small-molecule circadian rhythm modulators. The abilities of compounds to affect oscillations have received significant attention. We outline assessments of circadian changes using indirubin-3’-oxime (IO), 5-iodo-indirubin-3’-oxime (5I-IO), and 5-sulfonic acid-indirubin-3’-oxime (5SA-IO), analyzing effects on Bmal1 and Per2 oscillations and oncogenic features.

Glioblastoma (GB) is the most frequent malignant brain tumor among adults and currently there is no effective treatment. It is a very aggressive tumor that grows fast and spreads through the brain causing the death of patients in 15 months. GB cells mutate frequently and generate a heterogeneous population of tumoral cells genetically distinct. Thus, the contribution of genes and signaling pathways relevant for GB progression is of great relevance. We use a Drosophila model of GB that reproduces the features of human GB, and describe the upregulation of the circadian gene cry in GB patients and in a Drosophila GB model. We study the contribution of cry to the expansion of GB cells, to the neurodegeneration caused by GB, and to premature death and determine that cry is required for GB progression. Moreover, we analyze the mechanisms that regulate cry expression by the PI3K pathway. Finally, we conclude that cry is necessary and sufficient to regulate myc expression in GB. These results contribute to the understanding of the signals that impulse GB malignancy and lethality and open novel opportunities for the treatment of GB patients.

In mice, mutations or targeted disruptions of the core circadian gene Bmal1 have been implicated in early onset of ocular pathologies, including premature/congenital cataract development. The aim of the present study was to analyze probands of consanguineous Pakistani cataract families to identify the novel pathogenic variants in the BMAL1 gene. We have studied 21 congenital cataract families. Ophthalmic examination was performed for the probands and available family members. Genomic DNA was isolated from peripheral blood. PCR and Sanger sequencing was performed for the entire coding region of the BMAL1 gene. Targeted Sanger sequencing of BMAL1 revealed a heterozygous variant c.41A>T; p.(Asp14Val) in one proband, but it did not co-segregate with the disease phenotype in the family. In addition, a nonsynonymous variant (rs2290037) was identified in five probands. Our study is the first one to analyze the role of BMAL1 gene mutations in humans for their association with congenital cataract. Although we were unable to find the variants associated with congenital cataract families from Pakistan, more studies from other populations will be informative to further prove the role of BMAL1 with the disease.

Exosome-based therapy has emerged as a promising strategy for addressing diverse disorders, indicating the need for further exploration of the potential therapeutic effects of the exosome cargos. This study introduces "enhanced exosomes," a novel type of exosomes developed through a novel cell culture system. These specific exosomes may become potent therapeutic agents for treating ovarian disorders. In this study, we conducted a comparative analysis of the protein and miRNA cargo compositions of enhanced exosomes and naïve exosomes. Our findings revealed distinct cargo compositions in enhanced exosomes, featuring upregulated proteins such as EFEMP1, HTRA1, PAM, RSU1, and SDF4, suggesting their potential for treating ovarian disorders. MicroRNA profiling revealed that miR-1-3p, miR-103a-3p, miR-122-5p, miR-1271-5p, miR-133a-3p, miR-184, miR-203a-3p, and miR-206 are key players in regulating ovarian cancer and chemosensitivity by affecting cell cycle progression, cell proliferation, and cell development. We examined polycystic ovary syndrome and premature ovarian insufficiency and identified altered expression of various miRNAs, such as miR-106a-5p, miR-130b-5p, and miR-130b-3p, for diagnostic insights. This study highlights the potential of enhanced exosomes as new therapeutic agents for women's reproductive health, offering a detailed understanding of the impact of their cargo on ovarian disorders.

In the brain, astrocytes regulate shape and functions of the synaptic and vascular compartments through a variety of released factors and membrane-bound proteins. An imbalanced astrocyte activity can therefore have drastic negative impacts on brain development, leading to the onset of severe pathologies. Clinical and pre-clinical studies show alterations in astrocyte cell number, morphology, molecular makeup and astrocyte-dependent processes in different affected brain regions in neurodevelopmental (ND) and neuropsychiatric (NP) disorders. Astrocytes proliferate, differentiate and mature during the critical period of early postnatal brain development, a time window of elevated glia-dependent regulation of a proper balance between synapse formation/elimination, which is pivotal in refining synaptic connectivity. Therefore, any intrinsic and/or extrinsic factors altering these processes during the critical period may result in an aberrant synaptic remodelling and onset of mental disorders. The peculiar bridging position of astrocytes between synaptic and vascular compartments further allows them to “compute” the brain state and consequently secrete factors in the bloodstream, which may serve as diagnostic biomarkers of distinct healthy or disease conditions.Here, we collect recent advancements regarding astrogenesis and astrocyte-mediated regulation of neuronal network remodelling during early postnatal critical periods of brain development, focusing on synapse elimination. We then propose alternative hypotheses for an involvement of aberrancies in these processes in the onset of ND and NP disorders. In light of the well-known differential prevalence of certain brain disorders between males and females, we also discuss putative sex-dependent influences on these neurodevelopmental events.From a translational perspective, understanding age- and sex-dependent astrocyte-specific molecular and functional changes may help to identify biomarkers of distinct cellular (dys)functions in health and disease, favouring the development of diagnostic tools or the selection of tailored treatment options for male/female patients.

Recent evidence suggests the existence of shared neural resources for rhythm processing in language and music. Such overlaps could be the basis of the facilitating effect of regular musical rhythm on spoken word processing previously reported for typical children and adults, as well as adults with Parkinson’s disease and children with developmental language disorders. The present study builds upon these previous findings by examining whether musical rhythmic priming also influences visual word processing, and the extent to which such cross-modal priming effect of rhythm is related to individual differences in musical aptitude and reading skills. EEG was recorded while participants listened to a rhythmic tone prime, followed by a visual target word with a stress pattern that either matched or mismatched the rhythmic structure of the auditory prime. Participants were also administered standardized assessments of musical aptitude and reading achievement. ERPs elicited by target words with a mismatching stress pattern showed an increased fronto-central negativity. Additionally, the size of the negative effect correlated with individual differences in musical rhythm aptitude and reading comprehension skills. Results support the existence of shared neurocognitive resources for linguistic and musical rhythm processing, and have important implications for the use of rhythm-based activities for reading interventions.

Circadian rhythm disruptions are a hallmark feature of mood disorders. Patients experiencing acute depressive episodes report noticeable changes in their sleep-wake cycles. This research explains the association between depression and various circadian rhythm metrics, explicitly focusing on adolescents diagnosed with depressive disorders. Adolescence is a critical period marked by significant physiological and psychological changes, making it imperative to understand how mood disorders manifest during this phase. However, there have been minimal specific studies in pediatric populations to determine whether circadian rhythm changes differ between adolescents with first- and multiple-recurrent depressive episodes. Our study involved a group of 61 adolescents aged between 13 and 18. We performed a cross-sectional study of a clinical popu-lation of patients presenting to a child and adolescent psychiatry clinic diagnosed with depression. Participants were asked to complete self-report evaluations using several tools: The Korean ver-sion of the Biological Rhythms Interview of Assessment in Neuropsychiatry (K-BRIAN), the Korean Translation of Composite Scale to Measure Morningness-Eveningness (KtCS), and the Seasonal Pattern Assessment Questionnaire (SPAQ). Tools such as the Children's Depression In-ventory (CDI), State-Trait Anxiety Inventory (STAI), and K-Mood Disorder Questionnaire (K-MDQ) were employed for the assessment of clinical characteristics of depression. Based on the frequency of their depressive episodes, participants were bifurcated into two distinct groups: those experi-encing their first episode (n=22, mean age: 15.09±1.44 years) and those with recurrent episodes (n=39, mean age: 15.95±1.26 years). At first, the two groups' data revealed no significant differences regarding mood or circadian rhythm metrics (CDI: first-episode 26.18±10.54 and recurrent episode 25.90±10.59, STAI-S: first-episode 56.91±12.12 and recurrent episode 57.49±11.93, STAI-T: first-episode 60.36±11.63 and recurrent episode 59.09±12.10, SPAQ-total: first-episode 6.59±4.86 and recurrent episode 6.77±5.23, KtCS: first-episode 30.32±5.83 and recurrent episode 28.13±7.36). However, we observed significant correlations between circadian rhythm disruptions and depression scales (CDI with SPAQ-weight (r=0.26), KtCS (r=-0.48), K-BRIAN-sleep (r=0.58), K-BRIAN-activity (r=0.64), K-BRIAN-social (r=0.71) and K-BRIAN-eating (r=0.40)). These correlations were especially pronounced in the recurrent episode group, suggesting that with the progression and chronicity of depression, the relationship between circadian rhythms and depression becomes more intertwined and evident. In conclusion, especially in adolescents, as the severity and chronicity of depression increase, the interplay between circadian rhythms and mood disorders becomes more pronounced, warranting further research and clinical attention.

The article discusses early diagnosis and intervention for developmental delays in children, emphasizing the role of specialized services and personnel in supporting recovery and development. It presents findings from a pilot project initiated in Bucharest, aiming to assess the incidence of developmental delays in children aged 1-3 years in selected kindergartens, including ASD. The study involved children, parents, and specialists, utilizing systematic behavior observation (SBO) and semi-structured interviews. Results indicate that out of 613 evaluated children, 81 received specialized control recommendations, with 4 cases showing potential risk of ASD. Additionally, 8 children were diagnosed with autism. The incidence of autism in children aged 1-3 years was 1 in 51. Although exploratory, these findings suggest a model of good practice for future early diagnosis campaigns nationally. Conclusively, the study underscores the importance of early diagnosis and intervention for developmental delays, advocating for a responsive community and emphasizing the significance of national-level efforts to address these issues effectively.

In insects, Adipokinetic hormone is the primary hormone responsible for the mobilization of stored energy. While a growing body of evidence has solidified role of Adipokinetic hormone (AKH) in modulating the physiological and behavioral responses to metabolic stress, little is known about the upstream endocrine circuit that directly regulates AKH release. We evaluated the AKH-producing cell (APC) transcriptome to identify potential regulatory elements controlling APC activity, and found that a number of receptors show consistent expression levels, including all known dopamine receptors and the Pigment Dispersing Factor receptor (PDFR). We tested the consequences of targeted genetic knockdown and found that AKH expression of RNAi elements corresponding to each dopamine receptor caused a significant reduction in survival under starvation. In contrast, PDFR knockdown significantly extended lifespan under starvation whereas expression of a tethered PDF in APCs resulted in a significantly shorter lifespan. These manipulations caused various changes in locomotor activity under starvation. We used live-cell imaging to evaluate the acute effects of the ligands for these receptors on APC activation. Dopamine application led to a transient increase in intracellular calcium in a sugar-dependent manner. Furthermore, co-application of dopamine and ecdysone led to a complete loss of this response, suggesting that these two hormones act antagonistically. We also found that PDF application led to an increase in cAMP in APCs, and that this response was dependent on expression of the PDFR in APCs. Together these results suggest a complex circuit in which multiple hormones act on APCs to modulate metabolic state.

Chromothripsis is a mutational mechanism leading to complex and relatively clustered chromosomal rearrangements resulting in diverse phenotypic outcomes depending on the involved genomic landscapes. It may occur both in the germ and the somatic cells resulting in congenital and developmental disorders and cancer, respectively. Asymptomatic individuals may be carriers of chromotriptic rearrangements and experience recurrent reproductive failures when two or more chromosomes are involved. Several mechanisms are postulated to underly chromothripsis. The most attractive hypothesis involves chromosome pulverization in micronuclei followed by incorrect reassembly of fragments through DNA repair to explain the clustered nature of the observed complex rearrangements. Moreover, exogenous or endogenous DNA damage induction and dicentric bridge formation may be involved. Chromosome instability is commonly observed in the cells of patients with DNA-repair disorders, such as ataxia telangiectasia, Nijmegen breakage syndrome and Bloom syndrome. In addition, germline variations of TP53 have been associated with chromothripsis in Sonic-Hedgehog medulloblastoma and acute myeloid leukemia. In the present review, we focus on the underlying mechanisms of chromothripsis and the involvement of defective DNA-repair genes resulting in chromosome instability and chromothripsis-like rearrangements.

REV-ERBα and its paralog, REV-ERBβ encoded by NR1D1 and NR1D2 genes, are key nuclear receptors that link the circadian timing system and metabolic homeostasis. Since heme is an endogenous ligand, REV-ERBs have been considered key components of the circadian molecular clock that can be pharmacologically targeted to treat various circadian rhythm-related diseases, such as cardiometabolic, inflammatory, and neuropsychiatric diseases, as well as cancer. REV-ERBs are believed to be functionally redundant and compensatory, although they often affect the expression of gene subsets in an isoform-specific manner. Therefore, this study aimed to identify the redundant and distinct roles of each isoform in controlling its target genes by comparing the transcriptome profiles of a panel of mutant U2OS human osteosarcoma cells in which either NR1D1 or NR1D2 was ablated. Indeed, our transcriptomic analyses revealed that most REV-ERB-regulated genes were controlled by redundant or even additive actions. However, the RNA expression profiles of each single mutant cell line also provided strong evidence for isoform-dependent actions. For example, REV-ERBα were more responsible for regulating the NF-κΒ signaling pathway, whereas a group of extracellular matrix components required REV-ERBβ to maintain their expression. We found that REV-ERBs have isoform-selective functions in the regulation of certain circadian output pathways, despite their overlapping roles in the circadian molecular clock. Thus, the development of isoform-selective REV-ERB modulators may help treat metabolic disturbances and certain types of cancer.

Hypertensive diseases of pregnancy (HDP) represent a global clinical challenge, affecting 5-10% of women and leading to complications for both maternal well-being and fetal development. At the heart of these complications is endothelial dysfunction, with oxidative stress emerging as a pivotal causative factor. The reduction in nitric oxide (NO) bioavailability is a vital indicator of this dysfunction, culminating in blood pressure dysregulation. In the therapeutic context, although antihypertensive medications are commonly used, they come with inherent concerns related to maternal-fetal safety, and a percentage of women do not respond to these therapies. Therefore, alternative strategies that directly address the pathophysiology of HDP are required. This article focuses on the potential of the nitrate-nitrite-NO pathway, abundantly present in dark leafy greens and beetroot, as an alternative approach to treating HDP. The objective of this review is to discuss the prospective antioxidant role of nitrate. We hope our discussion paves the way for using nitrate to improve endothelial dysfunction and control oxidative stress, offering a potential therapy for managing HDP.

Neurofibromatosis type1 (NF1) is an autosomal dominant disorder caused by mutations in the NF1gene. Although congenital pseudarthrosis of the tibia (CPT) has frequently been associated with NF1, the underlying molecular mechanism of CPT in these NF1 patients is yet ill-understood. The aim of the present study was to detect NF1 mutations from genomic DNA and to harbor variants associated with CPT in NF1 patients. Whole-exome sequencing was first carried out with samples from two patients with CPT in one NF1 family, and a novel mutation c.2324A>G (p.E775G) in NF1 gene was identified. Additionally, a missense variant c.455C>T (p.P152L) in BCOR gene completely co-segregated with the CPT phenotype within this family. Subsequently, NF1 and NF2 genes in four other unrelated patients with both NF1 and CPT were screened using targeted sequencing. Four mutations in NF1 gene, including two known mutations (c.2288T>C/p.L763P, c.574 C>T/p.R192*) and two novel mutations (c.768delT/p.F256Lfs*25, c.2229_2230delTG/ p.V744Qfs*23) were detected. Further study confirmed that CPT was present in NF1 families, and NF1 mutations were closely associated with these complex phenotypes. Moreover, the data from the current study indicated that male gender might be a susceptibility factor for CPT in NF1. Therefore, we speculated that BCOR variants might be related to CPT phenotype among male NF1 patients.

Probiotics have been used to ameliorate gastrointestinal symptoms since ancient times. Over the past 40 years, probiotics have been shown to exert major effects on the immune system, both in vivo and in vitro. This interaction is clearly linked to gut microbes, their polysaccharide antigens, and key metabolites produced by these bacteria. At least four metabolic pathways have been implicated in mechanistic studies of probiotics, based on carefully studied animal models. Microbial-immune system crosstalk has been linked to short chain fatty acid production and signaling, tryptophan metabolism and the activation of aryl hydrocarbon receptors, nucleoside signaling in the gut, and activation of the intestinal histamine-2 receptor. Several randomized controlled trials have now shown that microbial modification by probiotics may improve gastrointestinal symptoms and multi-organ inflammation in rheumatoid arthritis, ulcerative colitis, and multiple sclerosis. Future work will need to carefully assess safety issues, selection of optimal strains and combinations, and attempts to prolong the duration of colonization of beneficial microbes.

Atrial fibrillation has progressively become a more common reason for emergency de-partment visits, representing 0.5% of presenting reasons. Registry data have indicated that about 60% of atrial fibrillation patients who present to the emergency department are admitted, emphasizing the need for more-efficient management of atrial fibrillation in the acute phase. Management of atrial fibrillation in the setting of emergency department varies between countries and health care systems. The most plausible reason to justify a conservative rather than aggressive strategy in the management of atrial fibrillation is the absence of specific guidelines from diverse societies. Several trials of atrial fibrillation treatment strategies, including cardioversion, have demonstrated that atrial fibrillation in emergency department can be treated safely and effectively, avoiding admission. In the present study, we review the epidemiology and characteristics of atrial fibrillation pa-tients presenting to the emergency department will be reviewed, as well as the impact of diverse management strategies on atrial fibrillation-related hospital admissions. Lastly, the design and initial data of the HEROMEDICUS protocol, which constitutes an elec-trophysiology-based aggressive rhythm control strategy in patients with atrial fibrillation in the emergency department setting will be presented.

Fetal Alcohol Spectrum Disorders (FASD) represent a continuum of lifelong impairments resulting from prenatal exposure to alcohol, with significant global impact. The “spectrum” of disorders includes a continuum of physical, cognitive, behavioral, and developmental impairments, which can have profound and lasting effects on individuals throughout their lives impacting their health, social interactions, psychological well-being and every aspect of their lives. This narrative paper explores the intricate relationship between oxidative stress and epigenetics in FASD pathogenesis and its therapeutic implications. Oxidative stress, induced by alcohol metabolism, disrupts cellular components, particularly in the vulnerable fetal brain, leading to aberrant development. Furthermore, oxidative stress is implicated in epigenetic changes, including alterations in DNA methylation, histone modifications, and microRNA expression, which influence gene regulation in FASD patients. Moreover, mitochondrial dysfunction and neuroinflammation contribute to epigenetic changes associated with FASD. Understanding these mechanisms holds promise for targeted therapeutic interventions. This includes antioxidant supplementation and lifestyle modifications to mitigate FASD-related impairments. While preclinical studies show promise, further clinical trials are needed to validate these interventions' efficacy in improving clinical outcomes for individuals affected by FASD. This comprehensive understanding of the role of oxidative stress on epigenetics in FASD underscores the importance of multidisciplinary approaches for diagnosis, management, and prevention strategies. Continued research in this field is crucial for advancing our knowledge and developing effective interventions to address this significant public health concern.

Electrocardigraphy remains as a first-line evaluation method for cardiac function, recording the electrical activity of the heart from the body surface. Since atrial activation is seen on the ECG as P-wave, several factors are known to impact the appearance of the P-wave, such as direction of electric impulse, conduction abnormalities and anatomical characteristics of the atria. The aim of this retrospective study was to find statistically significant associations between anatomy of pulmonary veins (PVs) osberved in cardiac computed tomography (CT) and P-wave appearance during sinus rhythm on resting ECG. For each patient, a resting 12-lead ECG was recorded, the field of analysis was P wave – its’ duration, morphology and axis. The evaluation of the CT scan recordings was performed by creating 3D models of the left atrium and analyzing anatomy of the PVs and left atrial appendage (LAA). Noteworthy correlations were found: anatomy of the left PVs showed an association with LAA volume, LAA morphology and P-wave notching in lead II. The right PVs demonstrated relation with P wave axis and amplitude. Although these correlations cannot be classified as strong, they may play a role in significant scientific discoveries in future research projects.

Among the many Lysosomal Storage Disorders (LSDs) that would benefit from the establish-ment of novel cell models, either patient-derived or genetically engineered, is Mucopolysaccha-ridosis type II (MPS II). In fact, even though a specific therapeutic approach does exist for this disorder (Enzyme Replacement Therapy, ERT, with recombinant human IDS) and haematopoiet-ic stem cell transplantation (HSCT) may also hold promise whenever the disorder is diagnosed soon enough, both approaches have their own drawbacks. Here we present our results on the establishment and characterization of two MPS II pa-tient-derived stem cell line(s) from deciduous baby teeth. To the best of our knowledge, this is the first time a stem cell population is isolated from LSD patient samples obtained from the oral cavity. Taking into account our results on the molecular and biochemical characterization of those cells and our first insights on their subcellular MPS phenotype, we consider these cells will be a valuable tool for both pathophysiological assessments and drugs screenings. Ultimately, we believe patient-derived dental pulp stem cells (DPSC) may represent a feasible alternative to induced pluripotent stem cells (iPSC) in many labs with standard cell culture con-ditions and limited (human and economic) resources.

This strategy had a very fast and good impact on the patient’s health; the CCM improved heart failure symptoms, hemodynamics flow and cardiac functionality. Moreover, after a relatively short time, the patient comes from persistent AF to Sinus Rhythm, although he starts with a severe bi-atrial dilatation. These parameters were stable during an extended follow-up of 18 months.

Exposure of experimental rodents to controlled cycles of light, food, and temperature is important when investigating alterations in circadian cycles that profoundly influence health and disease. However, applying such stimuli simultaneously is difficult in practice. Our aim was to design, build, test, and open-source describe a simple device that subjects a conventional mouse cage to independent cycles of physiologically relevant environmental variables. The device is based on a box enclosing the rodent cage to modify the light, feeding, and temperature environments. The device provides temperature-controlled air conditioning (heating or cooling) by a Peltier module and includes programmable feeding and illumination. All functions are set by a user-friendly front panel for independent cycle programming. Bench testing with a model simulating the CO2 production of mice in the cage showed: a) suitable air renewal (by measuring actual ambient CO2), b) controlled realistic illumination at the mouse enclosure (measured by a photometer), c) stable temperature control, and d) correct cycling of light, feeding, and temperature. The cost of all the supplies (retail purchased by e-commerce) was &lt; 300 US$). Detailed technical information is open-source provided, allowing for any user to reliably reproduce or modify the device. This approach can considerably facilitate circadian research since using one of the described low-cost devices for any mouse group with a given light-food-temperature paradigm allows for all the experiments to be performed simultaneously, thereby requiring no changes in the light/temperature of a general-use laboratory.

In vertebrates, oligodendrocytes (OLs) are glial cells of the central nervous system (CNS) responsible for the formation of the myelin sheath that surrounds the axons of neurons. The myelin sheath plays a crucial role in the transmission of neuronal information by promoting the rapid saltatory conduction of action potentials and providing neurons with structural and metabolic support. Saltatory conduction, first described in the peripheral nervous system (PNS), is now generally recognized as a universal evolutionary innovation to respond quickly to the environment: myelin helps us think and act fast. However, the function of myelin in the CNS, particularly in the brain, is not necessarily to act quickly, but rather to act correctly. In this respect, myelin should primarily play a role in synchronizing the different neuronal networks, a synchrony that occurs in the form of oscillations (or rhythms) relevant for specific information processing. Interestingly, myelin has been directly involved in different types of cognitive processes relying on brain oscillations, and myelin plasticity is currently considered to be part of the fundamental mechanisms for memory formation and maintenance. However, despite ample evidence showing the involvement of myelin in cognition and neurodevelopmental disorders characterized by cognitive impairments, the link between myelin, brain oscillations, cognition and disease is not yet fully understood. In this review, we aim to highlight what is known and what remains to be explored to understand the role of myelin in high order brain processes.

Peripheral tissue metabolism of steroids (intracrinology) is now accepted as a key way in which tissues, such as the endometrium, can utilize inactive steroids present in the blood to respond to local physiological demands and ‘fine-tune’ the activation or inhibition of steroid hormone receptor-dependent processes. Expression of enzymes that play a critical role in activation and inactivation of bioactive oestrogens (E1, E2) and androgens (A4, T, DHT), as well as expression of steroid hormone receptors, has been detected in endometrial tissues and cells recovered during the menstrual cycle. There is robust evidence that increased expression of aromatase is important for creating a local microenvironment that can support a pregnancy. Measurement of intra-tissue concentrations of steroids using liquid chromatography–tandem mass spectrometry has been important in advancing our understanding of a role for androgens in the endometrium acting both as active ligands for the androgen receptor and as substrates for oestrogen biosynthesis. The emergence of intracrinology, associated with disordered expression of key enzymes such as aromatase, in the aetiology of common women’s health disorders such as endometriosis and endometrial cancer has prompted renewed interest in development of drugs targeting these pathways opening up new opportunities for targeted therapies and precision medicine.

The circadian and stress-realizing systems are interconnected, and the balance of their interaction determines the state of human health. The objective of this study was to investigate the modulating effect of activating the circadian system on heart rate variability in female medical students with high anxiety while performing a cognitive task. After 20 minutes of adequate stimulation of circadian photoreceptors with a monochromatic blue light, the cognitive task performance resulted in a decrease in sympathetic impact. During the session of using Blue Sky Pro glasses, a trend of increasing heart rate variability was observed in a state of relative rest (especially in the first 5 minutes). A comparative analysis of the parameters of the letter cancellation test before and after light exposure revealed a statistically significant increase in the indexes reflecting mental productivity, work accuracy, and concentration of attention. The results suggest an essential physiological role of the human circadian system in modulating the autonomic and psycho-emotional conditions, as well as cognitive functions of individuals with high anxiety. Our findings indicate the possibility of quickly correcting the balance in human systemic regulatory mechanisms using the activation of retinal circadian photoreceptors by blue light.

Background: Annual influenza epidemics are a serious public health problem, causing particularly severe morbidity and mortality in high-risk groups. The study aimed to understand Poles' attitudes and beliefs towards influenza vaccinations in the flu season of 2022–2023, analyze preferences and unmet needs regarding influenza vaccinations, and examine the perception and acceptance of the influenza vaccine among individuals at risk of flu complications. Methods: A cross-sectional survey-based study was carried out on a sample of 1446 respondents. The Google Forms questionnaire was created and disseminated electronically using social media and e-mail. The pre-test was performed at the beginning of the project. Results: The majority of respondents (71%) could identify "high-risk groups" recommended for influenza vaccination. Furthermore, it was observed that individuals aged 21 to 59 demonstrated a higher level of knowledge in this regard compared to those below 20 and above 65 years old, and individuals with higher and medium education levels were much better at identifying risk groups for influenza virus infection. The majority of respondents (52.01%) reported receiving influenza vaccination at some point in the past, with 32.12% receiving it in the 2022–2023 flu season and 41.09% in the 2021–2022 season. The majority of respondents declaring acceptance of the vaccine for the 2022-2023 season were in the high-risk group. Only 17.28% of respondents declared receiving both influenza and SARS-CoV-2 vaccines in the 2022-2023 season, with the vast majority being respondents from the "high-risk group" (p

(1) Background: Sleep disordered breathing represent a growing public health concern, especially among children and adolescents. Full-night polysomnography is considered the gold standard for diagnosing obstructive sleep apnea. Our goals are to identify personal and environmental risk factors for the onset and persistence of sleep respiratory disorders. We also want to investigate the differences in neuropsychological profiles; (2) Methods: This is an observational, retrospective cohort study. We collected information on adenoidectomy or adenotonsillectomy. We reviewed the clinical history and preoperative visits and collected data through a telephone questionnaire. Pediatric Sleep Questionnaire (PSQ) and the Pediatric Quality of Life Inventory (PedsQL) are questionnaires used for screening sleep respiratory disorders in children. The data were statistically analyzed it using SPSS version 22.0 for Windows (SPSS Inc., Chicago, IL); (3) Results: The study involved 138 patients, but only 100 parents participated. A higher percentage of patients with sleep disordered breathing were observed to have mothers who smoked during pregnancy. A smaller proportion of patients with sleep disordered breathing had a habit of using a pacifier. A rise in physical results is associated with a reduction in the PSQ at follow-up (p=0.051). An increase of overall academic achievement is associated with an average decrease in the PSQ at follow-up (p&lt;0.0001). A more significant proportion of patients undergoing adenotonsillectomy were observed to have a history of prematurity and cesarean birth (4) Conclusions: These results provide essential information on the effectiveness and effects of adenotonsillectomy intervention compared to adenoidectomy intervention and the factors associated with SDB in children undergoing these interventions.

Background: Bleeding disorders can be divided into three categories: congenital coagulation disorders (CCDs), antiplatelet induced bleeding disorders (APBDs) and anticoagulant induced bleeding disorders (ACBDs). Implant placement can be challenging in this kind of patients. The aim of this study is to provide evidence on implant surgery in patient with bleeding disorders and to generate some practical recommendations for clinicians. Material &amp; Methods: Pubmed/MEDLINE, Scopus, Web of Science and Cochrane Library databases were screened. The latest search was performed in July 2022. Case Reports, Case Series, Cohort Studies, Cross-Sectional Studies, Case Control Studies, Reviews, Consensus Reports, Surveys and Animal Studies were included in the analysis. Results: Seventeen articles on CCDs were found, fourteen on APBDs, twenty-six on ACBDs. Most of these articles were case report or case series. Patients with CCDs can be treated after the infusion of the missing coagulation factor. Patients with APBDs can be treated without withdrawing the therapy. Patients with ACBDs should be treated depending on the anti-coagulative medication. Conclusion: Despite the low level of evidence, dental implants can be safely placed in patients with bleeding disorders. However, careful preoperative evaluation and the adoption of local and post-operative bleeding control measures are mandatory.

Type2 diabetes(T2D) is a pervasive modern disease, classified as a metabolic disorder marked by hyperglycemia, hyperinsulinemia, and life-long threatening cardiovascular morbidities. Subclinical inflammation stands as the primary pathogenetic factor propelling T2D progression, correlated with heightened levels of proinflammatory cytokines. Immune cells serve as the prominent sources of cytokine production, and under diabetic conditions, they tend toward a proinflammatory phenotype, fostering chronic inflammation. This review zeroes in on the disrupted homeostasis characteristic of diabetic conditions, encompassing cytokines, hormones, and their interplay with altered immune function, all contributing to the onset of diabetic cardiovascular complications.

The article describes how atherosclerosis and coronavirus disease 19 (COVID-19) may affect each other. The features of this comorbid pathogenesis at various levels (vascular, cellular and molecular) are considered. A bidirectional influence of these conditions is described: the presence of cardiovascular diseases affects different individual susceptibility to viral infection. In turn, SARS-CoV-2 can have a negative effect on the endothelium and cardiomyocytes, causing blood clotting, secretion of pro-inflammatory cytokines, and thus exacerbating the development of atherosclerosis. In addition to the established entry into cells via ACE2 принимая во внимание его влияние на, other mechanisms of SARS-CoV-2 entry are currently under investigation, for example, through CD147. Pathogenesis of comorbidity can be determined by the influence of the virus on various links which are meaningful for atherogenesis: generation of oxidized forms of LDL, launch of a cytokine storm, damage to the endothelial glycocalyx, and mitochondrial injury. The transformation of a stable plaque into an unstable one plays an important role in the pathogenesis of atherosclerosis complications and can be triggered by COVID-19. The impact of SARS-CoV-2 on large vessels such as aorta is more complex than previously thought considering its impact on vasa vasorum. Current information on the mutual influence of the medicines used in the treatment of atherosclerosis and acute COVID-19 is briefly summarized

Dendritic cells (DCs) are the professional antigen-presenting cells that recognize and present antigens to naïve T cells to induce antigen-specific adaptive immunity. Among the T-cell subsets, T helper type 2 (Th2) cells produce the humoral immune responses required for protection against helminthic disease by activating B cells. DCs induce a Th2 immune response at a certain immune environment. Basophil, eosinophil, mast cells, and type 2 innate lymphoid cells also induce Th2 immunity. However, in the case of DCs, controversy remains regarding which subsets of DCs induce Th2 immunity, which genes in DCs are directly or indirectly involved in inducing Th2 immunity, and the detailed mechanisms underlying induction, regulation, or maintenance of the DC-mediated Th2 immunity against allergic environments and parasite infection. A recent study has shown that a genetic defect in DCs causes an enhanced Th2 immunity leading to a severe atopic dermatitis. We summarize the Th2 immune-inducing DC subsets, the genetic and environmental factors which involved in DC-mediated Th2 immunity, and current therapeutic approaches for Th2-mediated immune disorders. This review is to provide an improved understanding of DC-mediated Th2 immunity and Th1/Th2 immune balancing, leading to control over their adverse consequences.

New research points to a possible link between Autism Spectrum Disorder and the gut microbiota as many autistic children have co-occurring gastrointestinal problems. This review focuses on specific alterations of gut microbiota mostly observed in autistic patients. Particularly, the mechanisms through which such alterations may trigger the production of the bacterial metabolites or leaky gut in autistic people are described. Various altered metabolite levels were observed in autistic children, many of those were of bacterial origin such as short chain fatty acids (SCFAs), indoles and lipopolysaccharides. A less integrative gut-blood-barrier is abundant in autistic individuals. This explains the leakage of bacterial metabolites into the patients triggering new body responses or altered metabolism. Some other co-occurring symptoms such as mitochondrial dysfunction, oxidative stress in the cells, altered tight junctions in the blood brain barrier and structural changes in cortex, hippocampus, amygdala and cerebellum were detected. Moreover, this paper suggests that autism is associated with an unbalanced gut microbiota (dysbiosis). Although the cause-effect relationship between autism and gut microbiota is not yet well established, consumption of specific probiotics may represent a powerful tool to re-establish gut homeostasis and promote gut health. Diagnostic and therapeutic value of new biomarkers leading to the perturbation in the phenylalanine metabolism will be discussed.

Background: Evidence supports a causal relationship between circadian disturbance and impaired glucose homeostasis. Method: To determine the effect of a nursing educational intervention on improving healthy sleep, a parallel, open-label clinical trial in subjects with Impaired Fasting Glucose (IFG) or Type 2 Diabetes Mellitus (T2DM) and 18 and older was performed. Study variables were sex, age, fasting glucose, glycated hemoglobin A1c (HbA1c), Pittsburgh Sleep Quality Index (PSQI), sleep duration and efficiency, BMI, antidiabetic treatment and diet and physical exercise. An individual informative educational intervention was carried out following a bidirectional feedback method. It was intended to develop skills to improve sleep through 9 simple tips. An analysis of covariance was performed on all the mean centered outcome variables controlling for the respective baseline scores. Results: After the intervention, in the experimental group, PSQI dropped, the duration and quality of sleep increased. Further, a decrease in fasting glucose and in HbA1c levels was observed. Conclusion: The proposed intervention has proven to be effective to improve sleep quality, time, and efficiency and in only 3 months, to achieve a decrease in fasting glucose and HbA1c levels. These findings support the importance of sleep and circadian rhythms education focused on improving in T2DM or IFG.

The brain reciprocally communicates with the rest of the body via neural, endocrine, immune, and other systems. This is crucial for coordinating the complex behavioral and physiological responses needed to cope with the many challenges of life. The Anterior Cingulate Cortex (ACC) is a key brain structure involved in assessing rewards and threats, as well as activating appropriate responses. This is a dynamic process that depends on evolving needs and challenges. Important challenges include illness or injury. These typically involve inflammation and pain, which evoke neuroinflammatory processes in the brain to drive sickness behaviours. In the short term, sickness behaviours are considered adaptive, as they promote convalescence (e.g. low mood; lethargy, fatigue, social withdrawal), and enhanced threat appraisal (e.g. anxiety) to combat increased risk/vulnerability associated with sickness. Chronic inflammation, however, appears to remodel the system to inappropriately activate threat-coping responses, resulting in depressive and/or anxious phenotypes. These mood disorders are particularly pronounced in diseases and disorders associated with gut dysfunction, which feature chronic inflammation and altered ACC function. We propose that chronic inflammation remodels ACC physiology such that it errantly predicts heightened danger based on a mental model (a.k.a ‘schema’) of the world. This evokes chronic activation of threat-coping systems, including endocrine signaling (e.g. adrenaline), and anxiety. Inflammation can be driven by brain systems involving ACC, leading to a feedback-cycle that self-reinforces pathological states. This theory accounts for a wealth of clinical and preclinical data that implicate the ACC in disorders of mood and gastrointestinal function, and reveals a key player in the gut-brain axis that may represent a novel therapeutic target.

Obsessive–compulsive disorder (OCD) is believed to follow a waxing and waning course, often according to environmental stressors. During the COVID-19 pandemic, pre-existing OCD symptoms were reported to increase and to change from checking to washing behaviors, while new-onset symptoms were predominantly of the hoarding type. In the present study, we followed the evolution of OCD symptoms, anxiety, depression, and insight of illness in forty-six OCD patients throughout the pandemic. Clinical measures were collected at four different time points before and during the COVID-19 pandemic in Italy. Within-subject comparisons were used to compare clinical scale scores across time, and correlations were examined between patients' baseline characteristics and changes in clinical scores. We found that all clinical measures increased during the first Italian lockdown, with respect to the pre-pandemic values. Anxiety decreased during the temporary elimination of restriction provisions, whereas severity of OCD symptoms and insight returned to pre-pandemic values during the second mandatory lockdown. These results were observed only in two sub-groups of patients: those taking benzodiazepines and those with shorter illness duration. Our findings suggest the need of additional clinical attention to these specific sub-groups of OCD patients in case of particularly distressing circumstances, while pointing to a possible adaptive role of their OCD symptoms when the environment requires a higher care of hygiene and extraordinary supply of essential resources.

Gliomas are solid tumors of the Central Nervous System (CNS) that originated from different glial cells. The World Health Organization (WHO) classified these tumors into four groups (I-IV) with increasing malignancy. Glioblastoma (GBM) is the most common and aggressive type of brain tumor classified as a grade IV. GBM are resistant to conventional therapies with poor prognosis after diagnosis even when the Stupp protocol that combines surgery and radiochemotherapy is applied. Nowadays, few novel therapeutic strategies have been used to improve GBM treatment, looking for higher efficiency and lower side effects, but with relatively modest results. The circadian timing system temporally organizes the physiology and behavior of most organisms and daily regulates several cellular processes in organs, tissues, and even in individual cells, including tumor cells. The potentiality of the function of the circadian clock on cancer cells modulation as a new target for novel treatments with a chronobiological basis offers a different challenge that needs to be considered in further detail. The present review will discuss state of the art regarding GBM biology, the role of the circadian clock in tumor progression, and new chrono-chemotherapeutic strategies applied for GBM treatment.

Drug-induced movement disorders (DIMDs) are a group of neurological conditions caused by the use of certain medications. These disorders can significantly impact a person's quality of life and are essential to recognize and manage. This article provides an overview of the causes, symptoms, and treatment of DIMDs. DIMDs can manifest in various forms, including parkinsonism, tardive dyskinesia, dystonia, and akathisia. They are most commonly associated with medications such as neuroleptics, antidepressants, antipsychotics, antiemetics, and anticonvulsants. Risk factors for developing DIMDs include age, genetics, duration of medication use, and dose of medication. Symptoms of DIMDs can range from mild to severe and may include tremors, rigidity, bradykinesia, and involuntary movements. These symptoms can significantly impact a person's ability to perform daily activities and lead to social isolation and decreased quality of life. DIMD diagnoses are based on clinical evaluation, including a thorough medical history and physical examination. Imaging studies such as MRI or CT scans may also be used to rule out other possible causes of symptoms. Treatment of DIMDs involves the withdrawal of the offending medication if possible. Pharmacological treatments such as anticholinergic drugs, benzodiazepines, and dopamine agonists may also be used to manage symptoms. Non-pharmacological treatments such as physical, occupational, and speech therapy can also be beneficial. DIMDs are necessary neurological conditions that can significantly impact a person's quality of life. Early recognition and management of these disorders are essential for optimizing outcomes. Further research is needed to understand the underlying mechanisms of DIMDs better and to develop more effective treatments.

Background: Evidence suggests that there is substantial comorbidity between fibromyalgia and Axis II pathology (i.e., personality disorders - PDs). The aim of the current study was to find out the exact cluster (A, B, C) PDs or traits that are more prominent in FM and may be predictors of FM diagnosis. Methods: Data from 86 subjects (53 with FM and 33 controls without FM) was analyzed in an observational, cross-sectional, comparative study. The assessment of categorical PDs and traits was performed independently with the Structured Clinical Interview for Personality Disorders (SCID-II). Binary logistic regression was used to determine FM predictors among PDs traits. Results. Compared with controls, FM patients had higher rate of PDs diagnoses (56.7 vs 18.2%, P&lt;.001). However, the rate was significantly higher only for borderline PD diagnosis (28.3% vs 6.1% P&lt;.05). The binary logistic regression analysis showed that schizotypal and schizoid (cluster A), borderline (cluster B), and dependent (cluster C) personality traits may be significant predictors of fibromyalgia (Nagelkerke R2 = 0.415). Conclusions: Our results may reflect association of FM with personality traits of all three PD clusters: A (eccentric), B (dramatic), C (anxious). However, the most consistent evidence seems to be for borderline PD.

Many of the potential immune therapeutic targets are similarly affected in adult-onset neurodegenerative diseases such as Alzheimer’s (AD) disease, Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), but also in a seemingly distinct Niemann-Pick type C disease with primarily juvenile-onset. This strongly argues for an overlap in pathogenic mechanisms. The commonly researched immune targets include various immune cell subsets such as microglia, peripheral macrophages, or regulatory T cells (Tregs), the complement system, and other soluble factors. In this review, we will compare these neurodegenerative diseases from a clinical point of view and point out the common pathways and mechanisms of protein aggregation, neurodegeneration and/or neuroinflammation that could potentially lead to shared treatment strategies. We also describe the common therapeutic approaches in treating the immune dysfunctions in these disorders, moving from immunization to microbiome regulation and stem cell treatment.

Complex interactions between gene variants and environmental risk factors underlie the pathophysiological pathways in major psychiatric disorders. Autism Spectrum Disorder is a psychiatric condition in which susceptible alleles along with epigenetic memories contribute to the mutational landscape of the ailing brain. The present work reviews recent evolutionary, molecular, and epigenetic mechanisms potentially linked to the etiology of autism. First, we present a clinical vignette to describe clusters of maladaptive behaviors frequently diagnosed in autistic patients. Next, we microdissect brain regions pertinent to the nosology of autism as well as cell networks from the bilateral body plan. Lastly, we catalog a number of pathogenic environments associated with disease risk factors. This set of perspectives provides emerging insights into the dynamic interplay between epigenetic and environmental variation in the development of Autism Spectrum Disorders.

Anxiety disorders manifest in women more than in men by almost twofold. This narrative review aims to summarize the sex-related biological factors, which underpin anxiety, focusing on the interactions of sex and tryptophan/serotonin with anxiety.A literature search was conducted using Google Scholar, PubMed/MEDLINE, Scopus, and EMBASE databases from inception until December 31, 2017. This review shows that sex may interact with many serotonin functions thereby modulating anxiety, including 5-HT1A and 5-HT2C receptors, 5-HT transporter and central 5-HT concentrations and metabolism. Sex-steroids modulate the expression of serotonin transporter genes, creating a difference in serotonin availability. Sex and estrous cycle phases lead to varying anxiety responses to tryptophan depletion. Testosterone, progesterone and estrogen are important factors in mediating sex differences in serotonin responses to anxiety-generating behavioral tests. At prenatal levels, there are sex-related differences in the reciprocal relationships between serotonin and the HPA-axis, which modulate anxiety-like behaviors. Activated immune-inflammatory pathways induce indoleamine-2,3-dioxynease (IDO) and the tryptophan catabolite (TRYCAT) pathway thereby increasing tryptophan degradation and increasing the production of TRYCATs including kynurenine and quinolinic acid, which may create an overall anxiogenic effect. The effects of immune activation on IDO are significantly more pronounced in women than men and therefore females may show increased levels of anxiogenic TRYCAT following immune challenge. Aberrations in the IDO-activated TRYCAT pathway are found in pregnant females and parturients and are associated with increased anxiety levels in the postnatal period. The results of this review underscore the necessity of studying the associations between serotonin and anxiety in both sexes taking into account the effects of immune activation on IDO and production of anxiogenic TRYCATs. Future anxiety research should focus on the interactions between serotonin/tryptophan and sex, sex hormones, the menstrual cycle, pregnancy, the HPA axis and the immune system through production of anxiogenic TRYCATs.

Recent research has highlighted associations between sleep and microbial taxa and pathways. However, the causal effect of these associations remains unknown. To investigate this, we performed a two-sample bidirectional Mendelian randomization (MR) analysis using summary statistics of genome-wide association studies (GWAS) from 412 gut microbiome traits (N = 7,738) and GWAS studies from seven sleep-associated traits (N = 345,552 to 386577). We employed multiple MR methods to assess causality, with Inverse Variance Weighted (IVW) as the primary method. We further applied Cochran’s Q statistical analysis, MR-Egger intercept, and MR-PRESSO for heterogeneity and pleiotropy assessment, alongside a Bonferroni correction ((P

The calmodulin-binding transcription activators (CAMTAs) mediate transcriptional regulation of development, growth, and responses to various environmental stresses in plants. To characterize the biological processes of soybean CAMTA (GmCAMTA) family members in response to abiotic stress, we identified 15 GmCAMTA genes from soybean (Glycine max L.) and investigated their roles in the abiotic stress response. The transcriptions of GmCAMTAs exhibited distinct circadian regulation patterns and were expressed differently in response to salt, drought, and cold stresses, except ABA. Interestingly, the expression levels of GmCAMTA2, GmCAMTA8, and GmCAMTA12 were higher in stem tissue than in other soybean tissues. To determine the roles of GmCAMTAs in the regulation of developmental processes and stress responses, we isolated GmCAMTA2 and GmCAMTA8 cDNAs from soybean and generated Arabidopsis overexpressing transgenic plants. The GmCAMTA2-OX and GmCAMTA8-OX plants showed hypersensitivity to drought stress. The water in the leaves of GmCAMTA2-OX and GmCAMTA8-OX plants was lost faster than that in WT plants under drought stress conditions. In addition, stress-responsive genes in the GmCAMTA2-OX and GmCAMTA8-OX plants were down-regulated under drought stress conditions. Our results suggest that GmCAMTA2 and GmCAMTA8 genes are regulated by circadian rhythms and function as negative regulators in development and drought stress responses.

Metabolic disorders have become among the most serious threats to human health, leading to severe chronic diseases such as obesity, type 2 diabetes, non-alcoholic fatty liver disease, as well as cardiovascular diseases. Interestingly, despite the fact that each of these maladies has different physiological and clinical symptoms, they appear to share certain pathological traits such as intracellular stress and inflammation induced by metabolic derangements stemmed from over nutrition frequently aggravated by modern sedentary life style. These modern ways of living inundate cells and organs with saturating levels of sugar and fat, leading to glycotoxicity and lipotoxicity that induce intracellular stress signaling ranging from oxidative to ER stress response to cope with the metabolic insults [1]. In this review, we discuss the roles played by cellular stress and its responses in shaping metabolic disorders. We have summarized here current mechanistic insights explaining the pathogenesis of these disorders. These are followed by a discussion of the latest therapies targeting the stress response pathways.

Frontotemporal lobar degeneration (FTLD) belongs to a heterogeneous group of highly complex neurodegenerative diseases and represents the second cause of presenile dementia in individuals under 65. Frontotemporal-TDP is a subgroup of frontotemporal dementia characterized by the aggregation of abnormal protein deposits, predominantly transactive response DNA-binding protein 43 (TDP-43), in the frontal and temporal brain regions. These deposits lead to progressive degeneration of neurons resulting in cognitive and behavioral impairments. Limbic age-related encephalopathy (LATE) pertains to age-related cognitive decline primarily affecting the limbic system which is crucial for memory, emotions, and learning. Though distinct, emerging research suggests a potential overlap in pathogenic processes, with some cases of limbic encephalopathy displaying TDP-43 pathology. Genetic factors play a pivotal role in both disorders. Mutations in various genes, such as progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72), have been identified as causative in frontotemporal-TDP. Similarly, specific genetic variants have been associated with an increased risk of developing LATE. Understanding these genetic links provides crucial insights into disease mechanisms and the potential for targeted therapies.

Temporomandibular disorders (TMD) is a group of orofacial pain conditions which is the most common non-dental pain complaint in the maxillofacial region. Due to the complexity of the etiology and often cyclical nature of the disease, the diagnosis and management of TMD remain a challenge where consensus is still lacking in many aspects. While clinical examination is considered the most important process in the diagnosis of TMD, imaging may serve as a valuable adjunct in selected cases. Depending on the type of TMD, many treatment modalities have been proposed, ranging from conservative options to open surgical procedures. In this review, the authors discuss the present thinking in the etiology and classification of TMD, followed by the diagnostic approach and the current trend and controversies in management.

Movement disorders encompass a diverse group of neurological conditions characterized by abnormal voluntary or involuntary movements. These disorders can be classified broadly into hyperkinetic and hypokinetic disorders. Excessive, involuntary movements, including tremors, dystonia, chorea, and myoclonus characterize hyperkinetic disorders. Tremors are rhythmic, involuntary movements occurring at rest or during movement. Dystonia involves sustained muscle contractions, leading to twisting and repetitive movements or abnormal postures. Chorea manifests as brief, irregular, involuntary movements that flow from one body part to another. Myoclonus consists of sudden, brief muscle contractions, either spontaneous or in response to a stimulus. Hypokinetic disorders are characterized by a lack of movement or difficulty initiating movement, as seen in Parkinson's disease and Parkinsonism. Parkinson's disease is a progressive neurological disorder that primarily affects movement, causing tremors, stiffness, and difficulty with balance and coordination. Parkinsonism refers to a group of disorders with similar symptoms to Parkinson's disease but with different underlying causes. Diagnosing movement disorders involves a thorough clinical evaluation, including a detailed medical history and physical examination. Neuroimaging studies such as MRI, CT scans, and functional imaging techniques may be used to assess brain structure and function. Additionally, laboratory tests, including genetic testing and biochemical markers, can help diagnose certain movement disorders.

To evaluate whether the extent of cardiac damage in severe aortic stenosis (AS) might be associated with the occurrence of conduction system disorders after TAVI. A total of 153 symptomatic patients with severe AS who had a TAVI were categorized before the procedure according to the extent of cardiac damage: stage 1 (13.5%): no or LV damage; stage 2 (58.8%): left atrial/mitral valve damage, atrial fibrillation (AF); stage 3 (27.7%): low-flow state, pulmonary vasculature/tricuspid valve/RV damage. After TAVI, 34% of patients exhibited LBBB and 10% high-degree atrioventricular block (HD-AVB). No patient in group 1 developed HD-AVD whereas new LBBB was frequent in groups 2 and 3. Twenty-one patients presented with resolutive paroxysmal AF with a higher rate for each group increment (group 1: n=0, 0%; group 2: n=11,15.7%; group 3: n=10, 30.3%) (p = 0.012). Patients in group 3 had the higher rate of permanent pacemaker implantation (PPMI) (group 1: n=1, 6.3%; group 2: n=7,10%; group 3: n=9, 27.3%) (p=0.012). No patient in group 1 died during the hospital stay. In conclusion, cardiac damage staging of AS might help identify patients at higher risk of conduction disorders and PPMI requirement after TAVI.

Since the worldwide spread of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), treating taste and saliva secretory disorders associated with coronavirus disease 2019 (COVID-19) has become one of the most critical issues in the COVID-19 era. The aim of the present study was to update information on treatments being applicable to such oral symptoms and discuss their pathogenic mechanisms. Promising treatments include different types of methods using tetracycline, corticosteroid, zinc, stellate ganglion block, phytochemical curcumin, traditional herbal medicine, nutraceutical vitamin D, photobiomodulation, antiviral drug, malic acid sialagogue, chewing gum, acupuncture, and/or moxibustion. At present, however, fully validated treatments are still lacking for COVID-19-associated ageusia/dysgeusia/hypogeusia and xerostomia/dry mouth/hyposalivation. An appropriately selected treatment and oral healthcare should be provided to COVID-19 patients and survivors suffering from taste and saliva secretory disorders. Understanding of currently available treatment options is required for dental profes-sionals because they not only experience patients who were infected with SARS-CoV-2 or recov-ered from COVID-19 but first become aware of their abnormal taste and salivary secretion. By doing so, dentists and dental hygienists can play a crucial role in managing COVID-19-associated oral symptoms and contribute to improving the oral health-related quality of life of the relevant dental patients.

Disordered eating is a serious health concern globally. The etiology is complex and multidimensional and differs somewhat for each specific eating disorder. Several risk factors have been identified which include psychological, genetic, biochemical, environmental, and sociocultural factors. Poor body image, low self-esteem, teasing, family dynamics, and exposure to media images have also been identified as risk factors. While it is enticing to consider a single behavioral risk factor, doing so fails to consider the documented environmental, social, psychological, biological, and cultural factors that contribute to the development of an eating disorder in a multidimensional and complex integration that is undoubtedly unique to everyone. Focusing only on any one factor without taking the complex etiology into account is remiss. For example, it has been suggested that the use of dietary supplements may lead to eating disorders, despite a lack of evidence to support this conjecture. Therefore, the purpose of this review is to examine the evidence-based risk factors for eating disorders and discuss why connecting dietary supplements to eating disorder etiology is not supported by the scientific literature and may interfere with treatment. Established, effective prevention and treatment approaches for eating disorders should be the focus of public health initiatives in this domain.

Age-related disorders of the musculoskeletal system including sarcopenia, osteoporosis and arthritis represent some of the most common chronic conditions worldwide, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. Collectively, these conditions involve multiple tissues, including skeletal muscle, bone, articular cartilage and the synovium within the joint lining. In this review, we discuss the potential for oligonucleotide therapies to combat the unmet clinical need in musculoskeletal disorders by evaluating the successes of oligonucleotides to modify candidate pathological gene targets and cellular processes in relevant tissues and cells of the musculoskeletal system. Further, we discuss the challenges that remain for the clinical development of oligonucleotides therapies for musculoskeletal disorders and evaluate some of the current approaches to overcome these.

Neurological / neurovascular disorders constitute the leading cause of disability and second leading cause of deaths in the world. Some of the major neurological / neurovascular disorders or diseases include stroke, Alzheimer’s disease, spinal cord injury, neonatal hypoxic-ischemic encephalopathy, etc. Their pathophysiology is considered as highly complex and has been blamed as the main obstacle in the development of any drugs for these diseases. In this review, we have described the endothelin system, their involvement in neurovascular disorders, importance of endothelin B receptors (ETBRs) as a novel potential drug target, and its agonism by IRL-1620 (INN - sovateltide), which we are developing as a drug candidate for treating the above-mentioned neurological disorders / diseases. We have highlighted the results of our pre-clinical and clinical studies related to these diseases. The phase I, safety and tolerability study of sovateltide has shown it as a highly safe and well tolerable compound at tested dosages, while pre-clinical and clinical phase II studies have demonstrated its efficacy in treating acute ischemic stroke, where it is currently being developed as a “First in Class” drug. Its testing in Alzheimer’s disease (AD), acute spinal cord injury and neonatal hypoxic-ischemic encephalopathy (HIE) is currently being carried out and are at different stages of drug development. Successful completion of these studies will prove the involvement of ETBRs signaling in neurological / neurovascular diseases and help in development of novel neurological drugs in future.

Apathy is a fundamental neuropsychiatric symptom of Korsakoff’s syndrome (KS) and has also been reported in patients with alcohol use disorder with no (AUD) or less severe cognitive disorders (ALC). However, research on the nature of apathy is limited in these groups. Aim of this study was to examine the multidimensional nature of apathy in patients with KS, ALC and AUD. Moreover, we examined differences between apathy ratings by patients and their professional caregivers, and related apathy to everyday functioning and overall cognition. Twenty-four patients with KS, 24 patients with ALC and 21 patients with AUD participated in this study. Apathy was measured using the Apathy Motivation Index (AMI), which distinguishes behavioral, emotional and social apathy. Both patients and professional caregivers reported social apathy as most prominent symptom, compared to behavioral and emotional apathy. Apathy ratings did not differ across the three patient groups. Discrepancies between patient and caregiver ratings were observed in patients with KS and ALC, with more severe apathy reported by caregivers. Caregiver-reported behavioral and social, but not emotional, apathy was related to everyday functioning. These results show that apathy is present in a substantial proportion of patients with alcohol addiction with or without cognitive impairments.

Smartwatches provide technology-based assessments in Parkinson’s disease (PD). We present results for sensor validation and disease classification via Machine Learning (ML). A comparison setup was designed with two different series of Apple smartwatches, one Nanometrics seismometer and a high-precision shaker to measure tremor-like amplitudes and frequencies. Clinical smartwatch measurements were acquired from a prospective study including 450 participants with PD, differential diagnoses (DD) and healthy participants. All participants wore two smartwatches and within a 15-min examination. Symptoms and medical history were captured on the paired smartphone. A broad range of different ML classifiers were cross-validated. Amplitude and frequency differences between smartwatches and the seismometer were under the level of clinical significance. The most advanced task of distinguishing PD vs DD was evaluated with 74,1% balanced accuracy, 86,5% precision and 90,5% recall by Multilayer Perceptrons. Deep Learning architectures significantly underperformed in all classification tasks. Smartwatches are capable of capturing subtle-tremor signs with low noise. This study provided the largest PD sample size of two-hand smartwatch measurements and our preliminary ML-evaluation shows that such a system provides powerful means for diagnosis classification and new digital biomarkers but it remains challenging for distinguishing similar disorders.

Psychiatric disorders are mental, behavioral or emotional disorders. These conditions are prevalent, one in four adults suffer from any type of psychiatric disorders world-wide. It has always been observed that psychiatric disorders have a genetic component, however new methods to sequence full genomes of large cohorts have identified with high precision genetic risk loci for these conditions. Psychiatric disorders include, but are not limited to, bipolar disorder, schizophrenia, autism spectrum disorder, anxiety disorders, major depressive disorder, and attention-deficit and hyperactivity disorder. Several risk loci for psychiatric disorders fall within genes that encode for voltage-gated calcium channels (Ca_Vs). Calcium entering through Ca_Vs is key for multiple neuronal processes. In this review, we will summarize recent findings that link Ca_Vs and their auxiliary subunits to psychiatric disorders. First, we will provide a general overview of Ca_Vs structure, classification, function, expression and pharmacology. Next, we will summarize tools and databases to study risk loci associated with psychiatric disorders. We will examine functional studies of risk variations in Ca_V genes when available. We will review pharmacological evidence of the use of Ca_V modulators to treat psychiatric disorders. Our review will be of interest for those studying pathophysiological aspects of Ca_Vs.

Background: Critical states present scale-free dynamics, optimizing neuronal complexity. We explored electroencephalogram (EEG) criticality in amnesic Mild Cognitive Impairment (aMCI) patients with clinical improvement in working memory, verbal memory, verbal fluency and overall executive functions after the completion of a 6-month prospective memory training. (2) Methods: We compared “before” and “after” stationary resting-state EEG records of right-handed MCI patients (n = 17; 11 females), using the method of critical fluctuations and Haar wavelet analysis. (3) Results: Significant criticality enhancement was present in frontotemporal electrodes [mean dif: 0.10; Z = 7, p = .019] and isolated electrodes T6 [mean dif: 0.204; t (10) = - 2.3, p = .044] and F4 [mean dif: 0.0194; t (10) = - 2.82; p = .018]. (4) Conclusions: EEG criticality agreed with clinical improvement, consisting a possible monitoring biomarker in MCI and Alzheimer’s disease. Further evaluation is needed in patients under cognitive training or even drug-modifying therapies.

Pancreatic β-cell-specific clock knock-out mice develop β cell oxidative-stress and failure, as well as glucose-intolerance. How inflammatory stress affects the cellular clock is under-investigated. Real-time recording of Per2:luciferase reporter activity in murine and human pancreatic islets demonstrated that the proinflammatory cytokine Interleukin-1β (IL-1β) lengthened the circadian period. qPCR-profiling of core clock gene expression in insulin-producing cells suggested that the combination of the proinflammatory cytokines IL-1β and Interferon-γ (IFN-γ) caused pronounced but uncoordinated increases in mRNA levels of multiple core clock genes, in particular of Reverse-erythroblastosis virus α (Rev-erbα), in a dose- and time-dependent manner. The REV-ERBα/β agonist SR9009, used to mimic cytokine-mediated Rev-erbα induction, reduced constitutive and cytokine-induced Brain and muscle arnt-like 1 (Bmal1) mRNA levels in INS-1 cells as expected. SR9009 induced reactive oxygen species (ROS), reduced insulin-1/2 (Ins-1/2) mRNA and accumulated- and glucose-stimulated insulin secretion, reduced cell-viability, and increased apoptosis levels, reminiscent of cytokine toxicity. In contrast low (<5,0 μM) concentrations of SR9009 increased Ins-1 mRNA and accumulated insulin-secretion without affecting INS-1 cell viability, mirroring low-concentration IL-1β mediated β-cell stimulation. Inhibiting nitric oxide (NO) synthesis, the lysine deacetylase HDAC3 and the immunoproteasome reduced cytokine-mediated increases in clock gene expression. In conclusion, the cytokine-combination perturbed the intrinsic clocks operative in mouse and human pancreatic islets and induced uncoordinated clock gene expression in INS-1 cells, the latter effect associated with NO, HDAC3 and immunoproteasome activity.

Psychotherapy is a comprehensive biological treatment modifying complex underlying cognitive, emotional, behavioral, and regulatory responses in the brain, leading patients with mental illness to a new interpretation of the sense of self and others. Psychotherapy is an art of science integrated with psychology and/or philosophy. Neurological science studies the neurological basis of cognition, memory, and behavior as well as the impact of neurological damage and disease on the functions, and their treatment. Both psychotherapy and neurological science deal with the brain; nevertheless, they continue to stay polarized far. Existential phenomenological psychotherapy (EPP) has been in the forefront of meaning-centered counseling for almost a century. The phenomenological approach in psychotherapy originated in the works of Martin Heidegger, Ludwig Binswanger, Medard Boss and Viktor Frankl, and it has been committed to account for the existential possibilities and limitations of one’s life. EPP provides philosophically rich interpretations and empowers counseling techniques to assist mentally suffering individuals by finding meaning and purpose of life. The approach has proven to be effective in treating mood and anxiety disorders. This narrative review article demonstrates the development of EPP, the therapeutic methodology, evidence-based accounts of its curative techniques, current understanding of mood and anxiety disorders in neurological science, and a possible converging path to translate and integrate meaning-centered psychotherapy and neuroscience, concluding that the existential phenomenological psychotherapy potently plays a synergistic role with the currently prevailing medication-based approaches for the treatment of mood and anxiety disorders.

Secondary movement disorders (SMDs) represent a heterogeneous group of neurological conditions characterized by abnormal, involuntary movements resulting from various underlying causes. This comprehensive review aims to thoroughly understand SMDs, including their epidemiology, pathophysiology, clinical manifestations, diagnostic approach, and management strategies. SMDs encompass a spectrum of movement abnormalities, including dystonia, chorea, athetosis, myoclonus, tics, and tremors. They can arise from a multitude of etiologies, such as drug-induced effects, post-infectious processes, metabolic disturbances, and structural brain lesions. The epidemiology of SMDs varies depending on the underlying cause, with some conditions being more prevalent in specific populations or age groups. Understanding the pathophysiology of SMDs is crucial for accurate diagnosis and targeted management. Diagnosing SMDs requires a comprehensive approach, including a detailed history, physical examination, laboratory investigations, neuroimaging studies, and sometimes electrophysiological studies. Management of SMDs is multifaceted and may involve pharmacological, non-pharmacological, and surgical interventions. Individualized treatment plans are essential, considering the underlying cause, severity of symptoms, and patient preferences. Emerging concepts in the field of SMDs include advancements in genetic research, identification of biomarkers, and development of novel therapeutic approaches. There is a growing focus on patient-centered care and improving the quality of life for individuals with SMDs. In conclusion, SMDs pose diagnostic and therapeutic challenges, requiring a multidisciplinary approach for optimal management. Continued research and collaboration are essential for advancing our understanding and treatment of these complex disorders.

Background and Objectives: Place the question addressed in a broad context and highlight the purpose of the study. Materials and Methods: Describe briefly the main methods or treatments applied, including the study population description. Results: Summarize the article’s main findings. Conclusions: Indicate the main conclusions or interpretations. The abstract should be an objective representation of the article, it must not) results. Meanwhile, exclusion criterion is incomplete data in medical record. For the analysis of continuous variables, a General Linear Model (univariate) was employed, with the predictors included specific Personality Disorder. The outcome being the PB, and covariates encompassed age, sex, education, clinical diagnosis, and depression score. Results: Six personality disorders, namely Paranoid, Schizoid, Histrionic, Avoidant, Dependent, and Obsessive-Compulsive Personality Disorder, did not exhibit significant pathogenic beliefs. In contrast, the remaining four personality disorders demonstrated significant associations with specific pathogenic beliefs. Conclusions: While some personality disorders have specific beliefs, it's also common to have pathogenic beliefs that are not specific to their psychodynamic. It's essential to recognize specific pathogenic beliefs for each individual to be targeted for their psychotherapy.

Here, we review findings and trends in sleep research in 2020-2021 demonstrating how COVID-19 and sleep disorders can induce the BBB leakage via neuroinflammation, which might contribute to the 'coronasomnia' phenomenon. The new studies suggest that the controlling of sleep hygiene and quality should be incorporated into the rehabilitation of COVID-19 patients. We also discuss perspective strategies for prevention of COVID-19-related BBB disorders. We demonstrate that sleep might be a novel biomarker of the BBB leakage and the analysis of sleep EEG patterns can be a breakthrough non-invasive technology for diagnosis of the COVID-19-caused BBB disruption.

Proper and timely segregation of cellular genome is an important and a prime requirement of all cell division programmes. Mis-segregation of chromosomes and resulting aneuploidy leads to several clinical consequences. Over the years, shugoshin emerges as a key protein factor involved in the segregation of genetic material in dividing cells. Deletion or altered level of shugoshin is reported in several human malignancies, as a result, shugoshin now emerges as an important tumour associated gene and a possible target for cancer therapy. Apart from the role in cancer, recent studies also showed the involvement of shugoshin in several other clinical disorders. Through this review, we tried to highlight the clinical relevance of shugoshin.

Term vascular dysfunctional refers to a wide spectrum of vascular abnormalities including pathogenesis of tumors, their proliferation and leading to malfunctioned conditions. The treatment of most of the vascular anomalies including peripheral arterial disease and cardiac disease is multi factor procedure which include the embolic therapy, laser-based treatments and coagulation are all plating important role in managing the disease associated with vascular breakdown. The research proposal defines the treatment and diagnosis procedures involved in treatment of vascular abnormalities with a deep emphasis on techniques, efficiency and complications resulted from various other procedure and use of mapping and sequencing techniques based on genetics of variants of selected genes PIk3CA which will ultimately be more effective.

Background: Hereditary hematologic disorders (HHDs) originate from genetic factors that cause disruptions of blood homeostasis. The Thalassemia Unit, Najaf province, Iraq, keeps all medical records of all patients with HHD from the Najaf province. Objectives: We aimed to conduct an epidemiological study to obtain a comprehensive epidemiological picture with regard to sex distribution, and effects of blood groups and consanguinity. Patients and Methods: All registered HHD patients (until May 2019) in the Thalassemia Unit (1122 patients, aged 0.5-65 years old) were included in the study. Results: The prevalence of HHD in Najaf city is 75.6 per 100,000 population. The number of patients registered as new patients is increasing over the years. There are significantly more male than female HHD patients (Male=54.37%, Female=45.63%, p=0.023). The top 3 prevalent HHD are Major thalassemia (33.15%), intermediate thalassemia (31.91%), and Thalassemia+Sickle (12.65%). The highest percentage of patients were in the center of Najaf (56.42%) followed by Kufa, Mishkhab, Haidariah, Manathera, and Abbasiya. The distribution of blood groups and Rh factors of HHD patients in the Najaf population was not significantly different from that in the normal population. The consanguinity rate observed in our patients' parents (78.24%) was significantly higher (p<0.0001) as compared with the consanguinity rate in the population (45.8%). Conclusions: During the last few years, there was an increase in HHD cases in Najaf city and, therefore, there is an urgent need to increase awareness about the effects of consanguinity marriages on HHD in order to limit the incidence of HHD.

Proteins play a pivotal role in supporting athletes by promoting muscle hypertrophy and minimizing protein catabolism during exercise. They stimulate muscle protein synthesis, aiding in the repair of exercise-induced muscle damage and serving as an energy source, particularly for post-exercise glycogen replenishment. In individuals with phenylketonuria (PKU), for whom protein intake is limited to essential phenylalanine (Phe), supplementation with Phe-free amino acids or glycomacropeptides is necessary. Tailored for macronutrient and micronutrient content, these protein substitutes fulfill most protein requirements, but lack Phe, unlike dietary sources of protein. Protein requirements for athletes with PKU exceed general recommendations due to limited availability in supplements and potential catabolism mitigation. Various factors influence tolerated dietary Phe in PKU, including protein substitute quantity, distribution, pharmacological treatment, age, growth rate, pregnancy, catabolic states, and physical activity. While general protein requirements for PKU surpass those of the general population, adherence to supplement regimens is crucial for athletes and patients with PKU. Strategically timed protein substitutes enhance muscle protein synthesis, body composition, and sports performance within safety limits. Individualized intake is essential for optimal outcomes, as proteins have a multifaceted role in optimizing athletic performance and addressing challenges in PKU.

Studies have established the crucial role of sleep among the students which plays a significant role in their mood. This study aimed to examine the mood disorders and sleep quality among undergraduate students at the University of Georgia (UG) and comparison between students’ nationality.This cross-sectional study was a self-reported questionnaire comprised of demographics including age, gender, year of study, current location, lifestyle data (Exercise and smoking), the Depression, Anxiety, and Stress Scale (DAS21) and the Pittsburgh Sleep Quality Index (PSQI). We performed a descriptive analysis, and the Chi-square was statistically significant at p<0.05. The prevalence was at a 95% confidence interval (95% CI) as multivariate analysis examined the multicollinearity. The female students were most of the respondents, below the age of 20 years. The student's mean age was 20.20 (SD± 3.0). DAS report presented 72.7% of students with depressive symptoms, 77.8% with anxiety symptoms, and 62.2% had stress. Georgian students were more at risk of having depressive complaints (95% Cl[1.567-3.788]), anxiety (95% Cl[1.612-4.285]), and stress symptoms (95% Cl[1.743-3.831]). There was a strong relationship between the students who experienced poor sleeping patterns and depressive complaints (aOR 0.10). The students who were smokers (aOR 0.39) were more likely to report anxiety symptoms than the students that do not exercise (aOR 1.68). It was observed that students with depressive symptoms, anxiety, and complaints of stress had a significantly high risk of poor sleep quality. Further studies are recommended to curb psychological symptoms of mood changes in association with sleep disorders among students.

Background: Despite tremendous efforts to reduce neonatal mortality worldwide and in 24 Ethiopia, there is the country is one of the countries with highest neonatal morbidity and health 25 losses. Never the less, the past three decades’ national trend and subnational distribution of 26 neonatal morbidity and mortality and its health loss in Ethiopia, was not well documented. 27 Hence, this study had aimed to analyze the trend and distributions as well as health losses 28 resulting from neonatal morbidity in the past three decades in Ethiopia, 2019. 29 Objective: To assess the national trend and sub national distributions of neonatal morbidity and 30 neonatal mortality in the previous three decades by using Global Burden of Diseases, 2019 data. 31 Methods: The data sources were primary and secondary data related to risk factors, morbidity, 32 disability, deaths, Disability Adjusted Life Years, Years Lived with Disability and Years Life Lost 33 were collected form case studies and case series, household surveys, socio-demographic surveys 34 and surveillances, health facilities surveys, Health facility observations and interviews and 35 published and unpublished literatures. The prevalence, deaths and health losses were calculated 36 by using embedded model. The study period covered from 1990 to 2019. Results were presented 37 buy using texts, tables and graphs. 38 Results: Seventy percent of neonatal disorders had occurred among early neonates aged 0 to 6 39 days. Between 1990 and 2019, the national prevalence of neonatal disorders had increased by 40 47% in to 28,319 (95% UI, 25646-30,361). Bet Similarly, the highest number of neonatal deaths 41 caused by neonatal sepsis had shifted from Southern Nations Nationalities and Peoples region to 42 Oromia region while Harari remains to bear the lowest burden in the last three decades. The 43 highest and the lowest YLL as a result of neonatal disorders had occurred in Oromia 44 [(2,753,038,95% UI, 2,184,142-3,497-926) and Amhara 1,360,847 [(95% UI, 95% UI, 45 1,062,660-1,762,028)] regions respectively. Unlike other regions, Addis Ababa had the highest 46 (52%) prevalence of preterm birth in 2019 47 Conclusion and Recommendation: About seven in ten of neonatal death had occurred among 48 early neonates indicating narrowed occurrence of the event. The highest and the lowest number 49 of neonatal death and health loss had occurred in Oromia and Harari regions respectively. The 50 main causes of death were neonatal sepsis and other infections, neonatal preterm, hemolytic 51 disease and other jaundice and neonatal encephalopathy and trauma. Hence, Contextualized, 52 locally accepted innovative early neonatal care is crucial to avert the event.

Chronic gastroduodenal symptoms are prevalent worldwide, and there is a need for new diagnostic and treatment approaches. Several overlapping processes may contribute to these symptoms, including gastric dysmotility, hypersensitivity, gut-brain axis disorders, gastric outflow resistance, and duodenal inflammation. Gastric Alimetry® (Alimetry, New Zealand) is a non-invasive test for evaluating gastric function that combines body surface gastric mapping (high-resolution electrophysiology) with validated symptom profiling. Together, these complementary data streams enable important new clinical insights into gastric disorders and their symptom correlations, with emerging therapeutic implications. A comprehensive database has been established, currently comprising >2,000 Gastric Alimetry tests, including both controls and patients with various gastroduodenal disorders. From studies employing this database, this pa-per presents a systematic methodology for Gastric Alimetry test interpretation, together with an extensive supporting literature review. Reporting is grouped into four sections: Test Quality, Spectral Analysis, Symptoms, and Conclusions. This review compiles, assesses, and evaluates each of these aspects of test assessment, with discussion of relevant evidence, example cases, limitations, and areas for future work. The resultant interpretation methodology is recommended for use in clinical practice and research to assist clinicians in their use of Gastric Alimetry as a diagnostic aid, and is expected to continue to evolve with further development.

The importance of a properly regulated immune response has been explored through various research-oriented methods. It has proved that having an effective and well-regulated immune response helps prevent many minors and serious diseases. Any kind of dysregulation in the working of the immune system may lead to severe consequences. An autoimmune disorder is one such consequence in which the component of the immune system starts targeting self-cells of the body, treating them as self-antigen producing autoantibodies and immune complexes resulting from the failure of immune responses both at a central and peripheral level. Currently, many autoimmune disorders are prevailing across the world, and new diseases need attention.In this review, we have written about the functions of T cell, LncRNAs and also some interactions between the LncRNAs and miRNAs in the pathogenesis of Multiple sclerosis (MS), Systemic lupus erythematosus (SLE), Type 1 diabetes (T1D), Rheumatoid arthritis (RA). To find the functions of these autoimmune disorders we have done intensive literature search during this we also found that GAS5 and MALAT are common in MS, SLE, T1D, RA. And finally, we have also mentioned the therapeutic drugs which neutralizes the different cluster of differentiation (CDs) and also suppresses the T cell differentiation in MS, SLE and RA. For T1D therapeutic strategies and various types of insulin are mentioned.

NF-κB is a central mediator of inflammation, response to DNA damage and oxidative stress. As a result of its central role in so many important cellular processes, NF-κB dysregulation has been implicated in the pathology of important human diseases. NF-κB activation causes inappropriate inflammatory responses in diseases including rheumatoid arthritis (RA) and multiple sclerosis (MS). Thus, modulation of NF-κB signaling is being widely investigated as an approach to treat chronic inflammatory diseases, autoimmunity and cancer. The emergence of COVID-19 in late 2019, the subsequent pandemic and the huge clinical burden of patients with life-threatening SARS-CoV-2 pneumonia led to a massive scramble to repurpose existing medicines to treat lung inflammation in a wide range of healthcare systems. These efforts continue and these efforts continue to be con-troversial. Drug repurposing strategies are a promising alternative to de-novo drug development, as they minimize drug development timelines and reduce the risk of failure due to unexpected side effects. Different experimental approaches have been applied to identify existing medicines which inhibit NF-κB that could be repurposed as anti-inflammatory drugs.

Abstract: Background: The Hospital-at-home (HAH) model is a viable alternative for conven-tional in-hospital stays worldwide. Serum electrolyte abnormalities are common in acute pa-tients, especially in those with many comorbidities. Pathologic changes in cardiac electrophysi-ology pose a potential risk during HAH stay. Periodical Electrocardiogram (ECG) tracing is therefore advised, but few studies evaluated the accuracy and efficiency of compact, self-activated ECG devices in the HAH settings. This study aimed to evaluate the reliability of such a device in comparison to a standard 12-lead ECG. Methods: We prospectively recruited consecu-tive patients admitted to the Sheba Beyond, virtual hospital, in the HAH department, during a 3-month duration. Each patient underwent a 12-lead ECG recording using the legacy device, and a consecutive recording by a compact 6-lead device. Baseline patients’ characteristics during hospi-talization were collected. Level of agreement between devices was measured by Cohen’s Kappa coefficient for inter-rater reliability (Ϗ). Results: Fifty patients were included in the study. 26 (52%) had electrolyte disturbances. Abnormal D-dimer values were observed in 33 (66%) pa-tients, and 12 (24%) patients had elevated troponin values. We found a level of 94.5% raw agreement between devices with regards to nine of the options included in the automatic read-out of the legacy device. The calculated Ϗ was 0.72, classified as substantial consensus. The rate of raw consensus regarding ECG intervals’ measurement (PR, RR, QT) was 78.5% and the calculated Ϗ was 0.42, corresponding to a moderate level of agreement. Conclusion: This is the first report to our knowledge regarding the feasibility of using a compact, 6-Lead ECG device in the setting of HAH to be safe and bearing satisfying agreement level with a legacy, 12-lead ECG device, en-abling quick, accessible arrythmia detection in this setting. Our findings bear a promise to the future development of telemedicine-based hospital at home methodology.

Cardiovascular morbidities are the main cause of mortality in pituitary disorders accruing either from hormonal excess or deficiency. Cushing disease is associated with various cardiovascular abnormalities;visceral obesity, insulin resistance, atherosclerosis, arterial hypertension, dyslipidaemia and hypercoagulability, structural and functional changes in heart, which do not seem to reverse completely even after remission. Acromegaly is related with insulin resistance, but also with structural and functional heart changes which consist acromegalic cardiomyopathy. Patients with prolactinomas demonstrate an aggravation of metabolic parameters, obesity, dysregulation of glucose and lipid metabolism and endothelial dysfunction. On the other hand, hypopituitarism and conventional hormonal replacement which is far from ideal contribute to an unhealthy metabolic status which leads to atherosclerosis and premature mortality. This review aims to update literature on cardiovascular risk and relevant morbidities in pituitary disorders.

SOX proteins are transcription factors which play a role in regulating the development of pro-genitor cells and tissue differentiation. Twenty members are known, clustered in eight groups named A to H, and sharing a common DNA-binding domain called the HMG (high-mobility-group) box. Eleven of the SOX genes have been associated with genetic disorders so far, covering a broad spectrum of developmental diseases. SOX4 is a single-exon gene and belongs to the SOXC group together with SOX11 and SOX12. SOX4 variants were recently described to cause a highly penetrant but heterogeneous disorder, with a phenotypic spectrum ranging from mild developmental delay and learning difficulties to intellectual disability with congenital anomalies. Nineteen pathogenic variants were reported to date, generally de novo, heterozygous, and inactivating, either stop-gain or missense, the latter ones primarily targeting the HMG domain. Further, a bi-allelic variant was reported in a single consanguineous family. Copy number variants, leading to whole gene deletion or duplication, are rare and not clearly associated with a neurodevelopmental disorder. Many open questions remain, regarding the definition of variants of unknown significance, a possible role of missense variants outside the HMG domain, genotype-phenotype correlation, the range of phenotypic spectrum and modifying factors, and treatment options.