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.

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.

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.

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.

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.

Global coverage and scale up of interventions to reduce newborn mortality remains low, though progress has been achieved in improving newborn survival in many low-income settings. An important factor in the success of newborn health interventions, and moving to scale, is appropriate design of community-based programs and strategies for local implementation. We report the results of formative research undertaken to inform the design of a newborn health intervention in Cambodia. Information was gathered on newborn care practices over a period of three months using multiple qualitative methods of data collection in the primary health facility and home setting. Analysis of the data indicated important gaps, both at home and facility level, between recommended newborn care practices and those typical in the study area. The results of this formative research have informed strategies for behavior change and improving referral of sick infants in the subsequent implementation study. Collection and dissemination of data on newborn care practices from settings such as these can contribute to efforts to advance survival, growth and development of newborns for intervention research, and for future newborn health programming.

In patients with primary central nervous system lymphoma (PCNSL), the choice of surgical strategy for histopathologic assessment is still controversial, particularly in terms of preoperative corticosteroid (CS) therapy. To provide further evidence for clinical decision-making, we retrospectively analyzed data from 148 consecutive patients who underwent surgery at our institution. Although patients treated with corticosteroids preoperatively were significantly more likely to require a second or third biopsy (p=0.049), it was only necessary in less than 10% of the cases with preoperative corticosteroid treatment. The choice of surgical procedure did not affect diagnostic accuracy (p>0.05). Preoperative CSF sampling did not provide additional information but was associated with delayed surgery (p=0.02). Surprisingly, diagnostic accuracy was significantly lower when patients were treated with anticoagulation or dual antiplatelet therapy (p=0.015). In conclusion, preoperative CS therapy can challenge the histological diagnosis of PCNSL. At the same time, our data suggest that preoperative CS treatment only presents a relative contraindication for an early surgical intervention. The standard surgical approach is stereotactic biopsy, but other approaches can be individually considered. If a definitive diagnosis cannot be made after the first surgical intervention, the timing of a repeat biopsy after discontinuation of CS remains a case-by-case decision.

The philosophy of testing statistical hypothesis is a natural consequence and functional extension of mathematical analysis of Probability. Along with the concept of recurrence when applied to random sequences and functions, it leads to the analysis of a priori and posterior which implies testing statistical hypothesis. Testing statistical hypothesis also involves algebraic, functional and dimensional considerations, which are found in the works of Laplace. Aspects of mathematical analysis such as universality of solutions, Laws of Large Numbers, Entropy, Information, and various functional dependencies are the main factors explained in the five properties that lead to implication of testing statistical hypothesis. Various interesting examples with modern scientific significance from genetics, astrophysics, and other areas give methodological access to answers of different problems and phenomena which are involved in the logic of testing statistical hypothesis.

Keywords: retinoblastoma, RB, gastric inhibitory polypeptide receptor, GIPR, trefoil factor family peptide, TFF1, CAM, tumorigenesis, MK0893, miR5-542-5p

This review focuses on the emerging evidence for the association between estimated cardiorespiratory fitness (eCRF) and metabolic risk factors. Given the challenges associated with directly measuring cardiorespiratory fitness (CRF) in large populations, eCRF presents a practical alternative for predicting metabolic health risks. A literature search identified six relevant cohort studies from 2021 to 2024 that investigated the association of eCRF with hypertension, hyperglycemia, dyslipidemia, and obesity. The review findings highlight a consistent inverse relationship between higher eCRF and lower incidence of metabolic risks in line with CRF cohort studies. This review highlights the importance of low eCRF as a primordial indicator for metabolic risks and underscores the need for broader application. Future research directions should include exploring eCRF's predictive accuracy across diverse populations and health outcomes and testing its real-world applicability in healthcare and public health settings.

(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.

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.

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.

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.

This study investigates the effect of perceived discrimination on the mental health of Afghan refugees, and secondly, tests the distress moderating effects of pre-migration traumatic experiences and post-resettlement adjustment factors. In a cross-sectional design, 259 Afghans completed surveys assessing perceived discrimination and a number of other factors using scales developed through inductive techniques. Multivariate analyses consisted of a series of hierarchical regressions testing the effect of perceived discrimination on distress, followed by a sequential analysis of moderator variables. Perceived discrimination was significantly associated with higher distress, and this relationship was stronger among those with a strong intra-ethnic identity, high civic engagement, and high pre-resettlement traumatic experiences. Discrimination is a significant source of stress for Afghan refugees, which may exacerbate stresses associated with other post-migration stressors. Future research is needed to tailor interventions that can help mitigate the stress associated with discrimination among this highly vulnerable group.

This study aimed to evaluate the safety and tolerability of STP1, a combination of ibudilast and bumetanide, tailored for the treatment of a specific subgroup of patients with Autism Spectrum Disorder (ASD), namely ASD Phenotype 1 (ASD-Phen1). We conducted a randomized, double-blind, placebo-controlled, parallel-group phase 1b study with two 14-day treatment phases (registered at clinicaltrials.gov as NCT04644003). Nine ASD-Phen1 patients were administered STP1, while three received a placebo. We assessed safety and tolerability, along with electrophysiological markers, such as EEG, Auditory Habituation, and Auditory Chirp Synchronization, to better understand STP1's mechanism of action. Additionally, we used several clinical scales to measure treatment outcomes. The results showed that STP1 was safe and well-tolerated, with electrophysiological markers indicating a significant and dose-related reduction of gamma power in the whole brain and in brain areas associated with executive function and memory. Treatment with STP1 also increased alpha 2 power in frontal and occipital regions and improved habituation and neural synchronization to auditory chirps. Although numerical improvements were observed in several clinical scales, they did not reach statistical significance. Overall, this study suggests that STP1 is safe and well-tolerated in ASD-Phen1 patients and shows indirect target engagement in ASD brain regions of interest.

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.

Neuropsychiatric disorders are globally public-health concern, in which diagnosis might be based on symptoms that often vary across individuals. Schizophrenia is one of the major neuropsychiatric disorders, which may affect millions worldwide. Detection of predictive biomarkers is the most intensively developing approach for the disease. However, the biochemical alterations have not been comprehensively distinguished up to the present time. In addition, there is less confidence of finding a specific biomarker for neuropsychiatric disorders including schizophrenia, but rather a specific characteristic behavioral pattern. Maternal immune activation has been considered to be one of the important factors for the development of neuropsychiatric disorders. Here, the mouse model of neuropsychiatric disorders has been built, in which poly-I:C, sodium dextran sulfate (DSS) and κ-carrageenan (CGN) were used for the maternal immune activation during the pregnancy of individuals. Subsequently, we challenged to link some of biochemical changes of p62 and GLAST in the offspring mice brain to the alteration of several pathological behaviors. Consequently, it has been shown that autophagy might be involved in the development of neuropsychiatric disorders including schizophrenia. To our knowledge, this is the first report of the significant correlation between pathological behavior and the biochemical alterations in neuropsychiatric disorder model animals. The relative ease of conducting these evaluation-tasks would make them useful for testing novel therapeutics designed to ameliorate the symptoms of several psychiatric disorders.

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.

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.

Insecurity, corruption, and rising unemployment have resulted in a mass exodus of young adult Afghans seeking asylum in western nations. This has depleted Afghanistan of generations of young people which are critical to rebuild the country. This study aimed to examine the characteristics of young adult Afghans with no immediate intentions of seeking international asylum; that is, individuals who intend to stay in Afghanistan. In a cross-sectional study conducted in Kabul, we surveyed 232 young adults between 18 and 35 years of age. Surveys included measures assessing standard socio-demographic and -economic factors, as well as health and psychological factors. Univariate logistic regression analyses suggest that participants with an intent to stay in Afghanistan are more likely to be financially stable, possess higher health-related quality of life, lower psychological distress, and higher levels of hope and optimism, as well as higher resilience. When controlling for all other variables in the model, only hope, optimism, and higher resilience remained as significant correlates of intending to stay. Our findings suggest that young people who intend to stay in their country look forward to a better future, which provides strong evidence for the need to strengthen the social contract by fostering resilience, hope and optimism in war-affected communities, in order to prevent a generation of talented young people from seeking asylum in western nations.

According to previous studies the median raphe region (MRR) is known to contribute significantly to social behavior. Beside serotonin, there are reports of a small population of dopaminergic neu-rons in this region. Dopamine is linked to reward and locomotion, but very little has been known about its role in the MRR. To address that, we first confirmed the presence of dopaminergic cells in the MRR of mice (immunohistochemistry, RT-PCR) and humans (RT-PCR). Next, we used chemogenetic technology in mice containing Cre enzyme under the promoter of the dopamine transporter (DAT). With the help of an adeno-associated virus, artificial receptors were expressed in the dopaminergic cells of the MRR (DAT-MRR). Four weeks later, extensive behavioral charac-terization started 30 minutes after the injection of the artificial ligand (Clozapine-N-Oxide). Stimu-lation of DAT-MRR decreased social interest without influencing aggression and with an increase in social discrimination. Additionally, inhibition of the same cells increased the friendly social be-havior during social interaction test. No behavioral changes were detected in anxiety, memory and locomotion. All in all, dopaminergic cells were present both in the mice and human MRR, and manipulation of dopaminergic neurons of the MRR elicited a specific social response.

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.

Definition: Most multicellular animals have a nervous system that is based on the following three components: 1) Sensory cells gather information and send it to processing units; 2) the processing units use the information to decide on what action to take; and 3) effector neurons activate the appropriate muscles. Due to the importance of making the right decisions, evolution made profound advances in the processing units. I shall review present knowledge regarding the evolution of neurological tools for making decisions, here referred to as strategies or algorithms. Consciousness can be understood as a particularly sophisticated strategy. It may have evolved to allow for the use of feelings as a ‘common currency’ to evaluate behavioral options. The advanced cognitive capacity of species such as humans further improved the usefulness of consciousness, yet in biological terms it does not seem to be an optimal, fitness-enhancing strategy. A model for the gradual evolution of consciousness is presented. There is a somewhat arbitrary cutoff as to which animals have consciousness but based on current information it seems reasonable to restrict the term to amniotes.

The Embodied Cognitive Behavior Therapy (ECBT) approach for the treatment of emotional disorders in clinical settings is presented. The model integrates cognitive behavioral theory, neuroscience and embodied cognition. ECBT draws from evidence of bidirectional effects between modes of bottom up (sensori-motor simulations giving rise to important basis of knowledge) and top down (abstract mental representations of knowledge) processes in psychotherapy. The paper first describes the dominance of the traditional mentalistic view of cognition and its limitations. Evidence for the embodied model of cognition and emotion is reviewed whilst highlighting its advantages as a complimentary process model to deepen and broaden talking therapies. An overview is given of the switch (e.g., the technique of balancing) between top-down and bottom-up orientation in the ECBT model as well as a clear description of the method for emotional regulation, acceptance of unwanted emotions and emotional mastery. ECBT builds on and extends the unconscious processes of the ‘Interpersonal Synchrony’ (IS) model identified by Koole and Tschacher [1], to enhance the therapeutic alliance for emotional co-regulation. A new idea is proposed that both embraces and extends the IS model: embodiment techniques of imitation and movement synchronization in the Emotional Field of our method be used in a conscious way to speed up the calming effects of co-regulation and the client’s self-regulatory capacity. The paper ends with an outline of the criteria needed to become an embodied therapist. A case study is given highlighting these aspects.

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.

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.

(1) Background: There is insufficient empirical evidence on the correlates of health care utilization of irregular migrants currently living in Turkey. The aim of this study was to identify individual level determinants associated with health service and medication use. (2) Methods: 155 Afghans completed surveys assessing service utilization including encounters with primary care physicians and outpatient specialists in addition to the use of prescription and nonprescription medicines. Multivariate logistic regression analyses were employed to examine associations between service use and a range of predisposing, enabling, and perceived need factors. (3) Results: Health services utilization was lowest for outpatient specialists (20%) and highest for nonprescription medications (37%). Female gender and higher income predicted encounters with primary care physicians. Income, and other enabling factors such as family presence in Turkey predicted encounters with outpatient specialists. Perceived illness-related need factors had little to no influence on use of services; however, asylum difficulties increased the likelihood for encounters with primary care physicians, outpatient services, and the use of prescription medications. 4) Conclusion: This study suggests that health services use among Afghan migrants in Turkey is low considering the extent of their perceived illness-related needs, which may be further exacerbated by the precarious conditions in which they live.

Pharmacists must acquire the necessary knowledge to provide better drug therapy to patients. In other words, educational programs need to facilitate behavioral changes among pharmacists. Therefore, this study aimed to evaluate how the behavior of pharmacists changed after attending a palliative care educational program. We conducted a web-based questionnaire survey examining the behavior of pharmacists regarding palliative care before participating in the program, two months after participating in the program, and eight months after participating in the program, to determine the behavior and changes over time. For all questions, scores were higher at two and eight months after attending the program than before attending the program (P <0.05). In addition, no significant difference was observed between two and eight months after attending the program for all questions (P =0.504-1.000). The knowledge gained from the educational program was used to repeatedly intervene with patients with cancer, to address the various symptoms they experienced and maintain their behavior. The proven effectiveness of this program serves as a stepping stone for a nationwide rollout across Japan’s 47 prefectures.

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.

Tinnitus is a common phantom auditory percept, believed to be related to plastic changes in the brain due to hearing loss. However, tinnitus can also occur in absence of any clinical hearing loss. Then, since there is no hearing loss, the mechanisms that drive plastic changes remain largely enigmatic. Previous studies showed subtle differences in sound-evoked brain activity associated with tinnitus in subjects with tinnitus and otherwise, normal hearing, but the results are not consistent across studies. Here, we aim to investigate those differences using monaural rather than binaural stimuli. Sound-evoked responses were measured using functional magnetic resonance imaging (MRI) in participants with and without tinnitus. All participants had clinically normal audiograms. The stimuli were pure tones with frequencies between 353 and 8000 Hz, presented monaurally. A Principal Component Analysis (PCA) of the response in the auditory cortex revealed no difference in tonotopic organization, which confirmed earlier studies. A GLM analysis showed hyperactivity in the lateral areas of the bilateral auditory cortex. Consistent with the tonotopic map, this hyperactivity mainly occurred in response to low stimulus frequencies. This may be related to hyperacusis, which was associated with tinnitus found in the parahippocampus. This may reflect an interference between tinnitus and spatial orientation.

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.

The industry is increasingly relying on fish for toxicity assessment. However, current guidelines for toxicity assessment focus on teratogenicity and mortality. From an ecotoxicological point of view, however, these endpoints may not reflect the “full picture” of possible deleterious effects that can nonetheless result in decreased fitness and/or inability to adapt to a changing environment, affecting whole populations. Therefore, assessing sublethal effects add relevant data covering different aspects of toxicity at different levels of analysis. Impacts of toxicants on neurobehavioral function have the potential to affect many different life-history traits, and are easier to assess in the laboratory than in the wild. We propose that carefully-controlled laboratory experiments on different behavioral domains – including anxiety, aggression, and exploration – can increase our understanding of the ecotoxicological impacts of contaminants, since these domains are related to traits such as defense, sociality, and reproduction, directly impacting life-history traits. The effects of selected contaminants on these tests are reviewed, focusing on larval and adult zebrafish, showing that these behavioral domains are highly sensitive to small concentrations of these substances. These strategies suggest a way forward on ecotoxicological research using fish.

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.

Patients with bipolar disorder (BD) experience more frequent and intense emotions in response to environmental conditions relative to healthy subjects, which leads to mood instability. The aim of this study was to investigate the time-course of emotion regulation strategies, distraction, and reappraisal, in euthymic BD patients using electroencephalography (EEG). Fourteen BD patients and 13 matched healthy controls took part in an experiment constituted of three conditions, i.e., a passive viewing of positive, negative, and neutral pictures and two regulation conditions, one with reappraisal strategy and the other with distraction strategy. Critically, ERP results indicated that during passive viewing, the Late Positive Potential (LPP) was larger in BD patients compared with healthy controls, but only for neutral pictures. During emotion regulation, LPP amplitude was reduced in distraction condition compared with viewing one, especially for negative emotions in both patients and controls. Importantly, LPP was reduced in reappraisal condition compared with passive viewing in an early time window for negative emotions and in a later time window for positive emotions in controls but not in patients. Our findings showed that the neurochronometry of emotion regulation is faster for negative than for positive emotion in controls but not in BD patients.

This article explores the behavioral geography of the Hajj pilgrimage, focusing on the impact of the physical environment on pilgrims' behavior. Using qualitative research and analyzing religious literature and online publications, the study reveals significant findings. The spatial arrangement of the Grand Mosque, including the central courtyard and pillars, influences pilgrims' behavior during the Tawaf ritual. Environmental factors such as crowds and noise affect pilgrims' experiences, evoking anxiety while enhancing the ceremony's spiritual significance. Cultural and religious beliefs also shape pilgrims' behavior during the circumambulation. This study provides valuable insights into the multifaceted factors shaping pilgrims' behavior during the Hajj, including spatial organization, cultural influences, and social interactions. The findings can inform improvements in infrastructure, crowd management, and services to enhance the overall pilgrimage experience.

Living organisms with developed endocrine systems react in a complex way to environmental changes. Changing atmospheric pressure causes different blood pressures or hormone levels; carcinogenic radiation modifies the structure of DNA. Charged particles and ions act as neurotransmitters and block certain types of protein channels and receptors. A high concentration of carbon dioxide has an indirect effect on both blood pressure and neuron activity. The bioelectric nature of living tissues highlights the complexity of the connection between the dynamic physical environment and biological systems. Recent results from studies on the interactions and connections mentioned above are reviewed in this paper.

The central nervous system (CNS) is the final frontier in drug delivery because of the blood-brain barrier (BBB), which poses significant barriers to the access of most drugs to their targets. Kynurenic acid (KYNA), a tryptophan (Trp) metabolite, plays an important role in behavioral functions and abnormal KYNA levels have been observed in neuropsychiatric conditions. The current challenge lies in delivering KYNA to the CNS owing to its polar side chain. Recently, C-3 side chain modified KYNA analogs have been shown to cross the BBB; however, it is unclear whether they retain the biological functions of the parent molecule. This study examined the impact of KYNA analogs, specifically SZR-72, SZR-104, and the newly developed SZRG-21, on behavior. The analogs were administered intracerebroventricularly (i.c.v.), and their effects on the motor domain were compared with those of KYNA. Specifically, open field (OF) and rotarod (RR) tests were employed to assess motor activity and skills. SZR-104 increased horizontal exploratory activity in the OF test at a dose of 0.04 μmol/4 μL, while SZR-72 decreased vertical activity at doses of 0.04 and 0.1 μmol/4 μL. In the RR test, however, neither KYNA nor its analogs showed any significant differences in motor skills at either dose. Side chain modification affects affective motor performance and exploratory behavior, as the results show for the first time. In this study, we showed that KYNA analogs alter emotional components such as motor-associated curiosity and emotions. Consequently, drug design necessitates the development of precise strategies to traverse the BBB while paying close attention to modifications in their effects on behavior.

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.

Research has shown that emotional states may influence the subjective experience of time. The present study involved 111 healthy adult participants and examined the impact of emotional stimuli on time perception, using a time estimation task with four conditions: in one of the conditions, participants estimated the exposure time of a black screen, wherein the duration could vary be-tween 2 to 7 s (condition without emotional interference); in the other conditions, participants es-timated the exposure time (also ranging from 2 to 7 s) of images that would induce pleasant, un-pleasant, or neutral emotions, to which participants were instructed to focus their attention (pleasant, unpleasant, or neutral emotions). The results showed that participants estimated “shorter” time intervals (underestimation) for pleasant and unpleasant images compared to the condition without interference, but no significant differences were found between the neutral condition and the condition without interference. It is suggested that increased attention to an ex-ternal stimuli, regardless of its emotional valence, produces an underestimated perception of time.

Aims: Adolescence is a critical period because the brain is involved in the process of maturation that entails cognitive functions. On the way of maturation, an individual’s inhibitory control undergoes many changes and becomes vulnerable to different thrill-seeking like smoking, drinking, and so on. Smoking is highly prevalent among teenagers that are trying to take control of their behaviors in order to join society. They experience antisocial behavior too which is a trait that can lead adolescents to addiction. This trait is an inevitable part of psychopathy. Inhibitory deficits and psychopathy have been widely reported in addiction studies. The current study tried to investigate the relationship between psychopathic traits and behavioral inhibition between male smokers and non-smoker teenage students.Materials & Methods: Statistical sample of this research is 62 teenage students aged 17 years that are divided into smoker and non-smoker groups. The participants have been chosen through random sampling from the population of 10 high schools. The data have been gathered in Kordkoy and Gorgan in Golestan province. Behavioral bias has been measured by Go/NoGo task and psychopathic traits through youth psychopathic traits inventory. Also, the short form of Wechsler Adult Intelligence Scale test has been executed and used as a control variable.Findings: A meaningful difference has been found between the performance of smoker and non-smoker groups in Go/No Go task and psychopathic traits that are smokers performed weaker in comparison with non-smokers and psychopathic traits of smokers were meaningfully higher than non-smokers. On the other hand, there was no significant difference between these two groups in their Wechsler Adult Intelligence Scale scores.Conclusion: The results have shown that smokers have higher psychopathic traits and lower behavioral inhibition when compared with their non-smoker peers. According to the results of current research, smoking can decline the cognitive functions.

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.

Alcoholic liver disease (ALD) is a major cause of chronic liver disease. This term covers a broad spectrum of liver lesions, from simple steatosis to alcoholic hepatitis and cirrhosis. The patho-genesis of ALD is multifactorial and not fully elucidated due to complex mechanisms related to direct ethanol toxicity with subsequent hepatic and systemic inflammation. The accumulation of pro-inflammatory cytokines and the reduction of anti-inflammatory cytokines promote the development and progression of ALD. To date, there are no targeted therapies to counteract disease progression and prevent acute liver failure. Corticosteroids reduce mortality by acting on the hepatic-systemic inflammation. On the other hand, several studies analyzed the effect of the inhibition of pro-inflammatory cytokines and the stimulation of anti-inflammatory cytokines as potential therapeutic targets in ALD. This narrative review aims to clarify the role of the cy-tokines in the pathogenesis and treatment of ALD.

Depression continues to be a glaring global challenge. The most worrisome trend is eating up the youthful generation more than anyone could predict years back. As Addis & Martell (2004) note, these adolescents end up succumbing to conditions that can be traced wholly from depression. Behavioral activation can be a rewarding intervention that will go a long way in cutting down on these cases and ensure the youthful global population's lives are safeguarded if applied and monitored to ensure correct and collective implementation processes and systems. The insights and arguments presented in the research paper will focus on the utility of behavioral activation in reducing depression cases among adolescents.

Superstar Learning System is an interactive information platform, where teachers and students can not only have an easy access to various learning resources, but also interact in the whole teaching and learning process. Although there have been a large number of studies devoted to the use of Superstar Learning System in education, very few of them explored its behavioral intention. In order to deal with this missing link in literature, we adopt a random sampling technique and a questionnaire survey to collect data. This study concludes that performance expectancy, effort expectancy, lecturer influence, peer influence, user innovativeness, interface simplicity, and multiple functions exert a positive influence on behavioral intention to use Superstar Learning System. We form a fit extended technology acceptance model (TAM) by including innovative constructs, i.e. lecturer and peer influences, user innovativeness, interface simplicity, and multiple functions. Interdisciplinary research is needed to explore an extended TAM to use Superstar Learning System in the future.

Conservation of natural habitats in human-dominated landscapes is critical for halting biodiversity loss. Maintaining habitat quantity and connectivity requires landscape-level collective action, which results from environmental decisions made by individual land owners. We investigate how individual decision making in a rural collective translates into quantitative differences in landscape-level environmental outcomes. Behavioral science has become a critical domain of knowledge in conservation, but little attention has been paid to how multiple behavioral drivers determine the success of collective environmental action. We developed a social-ecological model for landscape-level conservation using a detailed data set of 600 land owners in New Zealand. With the model, we tested whether the effect of social influence networks on collective conservation action was altered by their interplay with land owners’ personal characteristics, connections to cross-scale actors and local environmental contexts. Interactions between multiple behavioral drivers determined the environmental outcomes of collective action in unexpected ways by modifying, muting or amplifying the effects of single drivers. Importantly, we detected a social-ecological mechanism for rapid change in the extent of protected habitats, which can explain highly successful or failed environmental outcomes of collective conservation. Further, when environmentally desirable and undesirable behaviors spread simultaneously through the social network, homophily and network cohesion hinder desirable environmental outcomes. This effect can be modified by other drivers such as social responses to local environmental change. Thus, understanding how the antagonistic and synergistic effects of behavioral drivers can be best utilized in conservation will benefit biodiversity and ensure benefits that humans obtain from biodiversity.

Pediatric chronic pain is an important public health issue given its notable impact on numerous domains of living. Pediatric chronic pain is also often comorbid with emotional, developmental, or behavioral conditions which can lead to more severe negative outcomes and an even greater reduction in positive outcomes compared to those without comorbidities. Flourishing is a positive outcome that chronic pain status has been shown to impact. We explored flourishing in children aged 6-17 years living with chronic pain as well as those with chronic pain and comorbidities using data from the 2018/2019 National Survey of Child Health. There were significant associa-tions between chronic pain condition status and all demographic variables (sex, age, race/ethnicity, poverty level, parental education, health insurance status). Results of hierarchical logistic regression found that chronic pain condition status significantly predicted flourishing. Children with chronic pain were 2.33 times less likely to flourish, and children with chronic pain plus an emotional, developmental, or behavioral comorbidity were 13 times less likely to flourish than typical peers. Given their significantly lower likelihood of flourishing, there is an urgent need for interventions targeted at children experiencing chronic pain and mental health comor-bidities.

Colombia is noteworthy as a biodiversity hotspot, featuring an extraordinary number of en-demic orchids, birds, and butterflies. This exploratory study examines the perceptions of desti-nation image considering the cognitive and affective image in predicting behavioral intentions of ecotourists through symmetric data analysis. Using Partial Least Squares (PLS), the author(s) analyzed 64 survey responses collected of rural areas, including a new 15 statement scale spe-cialized on birdwatching. The findings support the reliability of the model, symmetric analysis presents the higher influence of emotions and affections in increasing intentions of recommen-dation, considering birdwatching as based on personal relationships. Additionally, the cognitive image for the birders despite representing destination attributes or sets of destination resources of a mental picture does not have the same impact on behavioral intentions. Therefore, manag-ers should develop positioning strategies based on the generation of emotions, because bird-watching tourists seek to have more emotional experiences.

Cartoons in the era of digital media are among the most prevalent medium of entertainment for the children, parents also encourage them to view such contents to engage the children which make an area need to be explained exhaustively by adopting new approaches. There are lot of studies in the past conducted to explain the impacts of the cartoons on the children however, it is remarkable fact that there is lack of the studies in the literature which directly address the observation about the above mentioned impacts in view of the teacher’s. This study deals with the educational, emotional, behavioral and Religious etc. impacts of cartoons on kids in view of teachers of the primary schools as they are considered as the one who can observer these impacts in a profound way. of the of Multan. Different areas of impacts have been analyzed in this study by using survey technique and analysis is conducted and presented in the teacher’s views in this study to examine what they feel that how cartoons are effecting the personalities of the children.

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 & 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.

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<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.

Pure silver as well as silver compounds have been used as antiseptics for centuries. Nowadays, the most frequently applied form of silver is a nanoparticle form. Several studies demonstrate the ability of silver nanoparticles and silver salts to accumulate in the brain of laboratory ani-mals as well as the ability of silver nanoparticles to influence behavioral and cognitive functions of laboratory mammals. For the first time, the influence of a silver salt, in particular, silver citrate on the change dynamics of behavioral and cognitive functions of laboratory mice at the daily oral exposure during 30, 60, 120 and 180 days is investigated in the present research. We observed the anxiety increase after 30 days of the exposure as well as the ability of mice to adapt to the prolonged oral exposure of silver citrate manifested in the anxiety decrease, increase of locomotor activity and the tendency of long-term contextual memory improvement. Increase of locomotor activity and memory improvement might be associated with the sensitivity increase and regarded as compensatory mechanism to anxiety increase. The observed phenomenon is classified as a hormetic effect. A comparison with the analogous study implemented polyvi-nylpyrrolidone coated silver nanoparticles is carried out. It was concluded that the nanoform is more neurotoxic.

The Gestalt psychologists’ theory of insight problem-solving was based on a direct parallelism between perceptual experience and higher-order forms of cognition (e.g., problem-solving). Simi-larly to the sudden recognition of an ambiguous figure, they contended that problem-solving in-volves a restructuring of one's initial representation of the problem’s elements, leading to a sud-den leap of understanding phenomenologically indexed by the "Aha!" feeling. Over the last centu-ry, different scholars discussed the validity of the Gestalt psychologists’ perspective foremost us-ing the behavioral measures available at the time. However, in the last 2 decades, scientists gained a deeper understanding of insight problem-solving due to the advancements in cognitive neuroscience. This review aims to provide a retrospective reading of Gestalt theory based on the knowledge accrued by adopting novel paradigms and investigating their neurophysiological correlates. Among several key points that the Gestalt psychologists underscored, we focus specif-ically on the role of the visual system in marking a discrete switch of knowledge into awareness, as well as the perceptual experience and the holistic standpoints. While the main goal of this paper is to read the previous theory in light of new evidence, we also hope to initiate an academic dis-cussion and encourage further research about the points we raise.

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.

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.

This research article aims to examine the factors that influence behavioral intentions using the traffic accident claim system in Indonesia. This research uses the Theory of Planned Behavior, the Model of Technology Acceptance, and the Integrated Theory of Technology Acceptance and Use, as well as using the Structural Equation Modeling-Partial Least Squares. The questionnaire was distributed to 580 respondents from three institutions – police, hospitals, and state-owned insurance companies – using quota sampling techniques. The results showed that TPB, TAM, and UTAUT had a significant influence in encouraging behavioral intentions using the traffic accident claim system. Further, the study found that 21st-century digital skills have a moderate role in the impact of acceptance models, planned behavior, and technology use on behavioral intent. Although the study was conducted in Indonesia and is limited to three institutions, it provides strategic guidance for policymakers to improve the use of traffic accident claim systems and reduce Road Traffic Accidents. Further research is recommended to explore from different angles and focus on service providers/operators of traffic accident claim systems to refine the findings of this study. This study contributes to the literature by investigating the factors that influence behavioral intentions using traffic accident claim systems and has a high degree of accuracy of answers from the point of view of traffic safety officers.

Predicting change from multivariate time series has relevant applications ranging from medical to engineering fields. Multisensory stimulation therapy in patients with dementia aims to change the patient’s behavioral state. For example, patients who exhibit a baseline of agitation may be paced to change their behavioral state to relaxed. This study aims to predict changes in behavioral state from the analysis of the physiological and neurovegetative parameters to support the therapist during the stimulation session. In order to extract valuable indicators for predicting changes, both handcrafted and learned features were evaluated and compared. The handcrafted features were defined starting from the CATCH22 feature collection, while the learned ones were extracted using a Temporal Convolutional Network, and the behavioral state was predicted through Bidirectional Long Short-Term Memory Auto-Encoder, operating jointly. From the comparison with the state-of-the-art, the learned features-based approach exhibits superior performance with accuracy rates of up to 99.42% with a time window of 70 seconds and up to 98.44% with a time window of 10 seconds.

Recently, medaka has been used as a model organism in various research fields. However, even though it possesses several advantages over zebrafish, fewer studies were done in medaka than zebrafish, especially its behaviour. Thus, to provide more information regarding its behaviour and to demonstrate the be-havioural differences between several species of medaka, we compared the behavioural performance and biomarker expression in the brain between four medaka fishes, which were Oryzias latipes, O. dancena, O. woworae, and O. sinensis. From the results, we found that each medaka species explicitly exhib-ited different behaviours to each other, which might be related to the different basal levels of several biomarkers. Furthermore, by phenomics and ge-nomic-based clustering, the differences between these medaka fishes were further investigated. Interestingly, even though both phenomics and ge-nomic-based clustering showed some resemblances to each other in terms of the interspecies relationship between medaka and zebrafish, however, in the medaka interspecies comparisons, this similarity was not displayed. Therefore, these results suggest a re-interpretation of several prior studies in comparative biology. We hope that these results contribute to the growing database of medaka fish phenotypes and provide one of the foundations for future phe-nomics studies of medaka fish.

Recent findings show that preferences for food items can be modified without external-reinforcements using the cue-approach task. In the task, the mere association of food item images with a neutral auditory cue and a speeded button press, resulted in enhanced preferences for the associated stimuli. Here, in a series of 10 independent samples with a total of 255 participants, we show we can enhance preferences using this non-reinforced method for faces, fractals and affective images as well as snack foods, using auditory, visual and even aversive cues. This change was highly durable in follow-up sessions performed one to six months after training. Preferences were successfully enhanced for all conditions, except for negative valence items. These findings promote our understanding of non-reinforced change, suggest a boundary condition for the effect and lay the foundation for development of novel applications.

Pathophysiology of depression is related with reduced volume of the hippocampus and amygdala and hypertrophy of the nucleus accumbens. The mechanism of these changes is not well under-stood, but clinical studies have shown that administration of the fast-acting antidepressant keta-mine reversed the decrease in hippocampus and amygdala volume in depressed patients, and the magnitude of this effect correlated with the reduction of depressive symptoms. In the present study, we attempted to find out whether the psychedelic substance psilocybin affects neurotransmission in the limbic system in comparison to ketamine. Psilocybin and ketamine increased the release of dopamine (DA) and serotonin (5-HT) in the nucleus accumbens of naive rats as demonstrated using microdialysis. Both drugs influenced glutamate and GABA release in the nucleus accumbens, hippocampus and amygdala and increased ACh levels in the hippocampus. The changes in D2, 5-HT1A and 5-HT2A receptor density in the nucleus accumbens and hippocampus was observed as a long-lasting effect. A marked anxiolytic effect of psilocybin in acute phase and 24 h post-treatment was shown in the open field test. These data provide the neurobiological background for psilocybin effect on stress, anxiety and structural changes in the limbic system and translate into antidepres-sant effect of psilocybin in depressed patients.

Online teaching is considered an important approach for achieving sustainable learning and education, and college teachers’ attitude and behavioral intention are essential for the sustainable adoption of online teaching practice in higher education institutions. To examine the influencing factors that sustain teachers’ attitude toward online teaching and behavioral intention, we conducted a cross-sectional study based on a sample of 1,102 college teachers in central China, using hierarchical linear regression analysis to explore possible influencing factors in four levels: individual experience, environmental support, self-perception, and technology acceptance. The study results show that the subjective norms, readiness, beliefs, and perceived usefulness of online teaching had a significant impact on teachers’ attitude toward online teaching and behavioral intention. Nevertheless, the effect varied with factors like online-teaching load and teachers’ technology self-efficacy, as their influence seemed to be singular, affecting the teachers’ attitude toward online teaching or behavioral intention exclusively. In contrast, previous online-teaching experience did not notably affect either. The findings of this study reveal the complex interactions of factors that influence college teachers’ disposition toward and decisions about online-teaching practices and emphasize the need for targeted strategies to maintain and enhance online education in the post-pandemic era.

Neurodevelopmental disorders are characterized by an amalgam of genetic and epigenetic faults implicating neuronal protein-related loss-of-function and gain-of-function respectively, hence their inclusion into the category of complex diseases. Neurodevelopmental disorders are regarded as autism spectrum disorder due to this reason; that the risk factors and phenotype constitute a spectrum of faults and protein overactivity. One example of an epigenetic factor leading to the onset of neurodevelopmental delays constitutes a set of immune response-based dysregulations, as well as the excessive growth of the adaptive immune memory of the fetus or the baby following significant infectious disease during pregnancy, as well as in babies aged 0-2, given the existence of profound links between developmental immunity and developmental neurology. Given that genetic information very likely represents a form of energy, the intake of excessive pathogen-related information may transiently overload the adaptive immune memory similarly to the manner functional pathogens do whilst inducing significant illness, and if events as such occur during important stages of neuro-immunological development, then there could often be irreversible effects upon the rate of development in neurological networks that normally have a major importance in the modulation of the related cognitive and behavioral phenotype. The full extent of evidence may only be obtained via a thorough study of the applications of physical laws into biology and medicine, given the foundational role of the physical matter in the development and maintenance of life. A common misconception is that neurodevelopmental delays are characterized solely by an accumulation of protein loss-of-function incidences in the central nervous system area, rather than a disruption of neuronal region developmental rates. For example, an overexpression of neuronal proteins related to cognition factors that is accompanied by an underexpression of proteins related to social behavior is phenotypically manifested in people with sharper rational thinking and poorer communication skills, with an impact on the abilities of decision-making as well, and this tends to be regarded as a classical example of the clinical manifestation of neurodevelopmental delays. More severe forms of autism spectrum disorder tend to implicate a more generalistic impact upon the developmental rates of key human behaviors, including those related with the development and maintenance of social and intimate relationships. Likewise, more severe implications upon regular developmental rates tend to bring a major impact upon the healthy function of related functions. As a result, lower functioning forms of neurodevelopmental delays bring fresh concerns with regards to a possible uncanny increase of incidences of deviated sexuality during years of adulthood, and in the worst cases, such deviations may lead to the planning and development of criminal activity, particularly in individuals who are or become prone to breaking the moral code that established the civilized society. What holds the concerns valid is the exponential increase in the number of lower functioning autism cases throughout the world and the major signs that such an increase will continue with a full force. One major solution to this potential future problem would be a much higher investment into awareness of the exact genetic and environmental factors that directly or indirectly result in the onset of lower-functioning autism and of the current research efforts to develop the matching support for people found in situations as such. The most important aim of future research with regards to such a scenario would be a separation of disease and disability with choices made to step into more severe forms of disease and into areas that are outside of the established moral circle.

Oxytocin (OXT), a pro-social peptide, is increasingly recognized as a potential protective substance against drug addiction. In the context of ethanol, previous researches have shown OXT properties to reduce self-administration, alleviate motor impairment in rodents, and reduce craving in humans. However, its role in behavioral sensitization, a neuroadaptive response resulting from repeated drug exposure linked to increased drug incentive, remains unexplored. OXT is also associated with modulating the Hypothalamic-Pituitary-Adrenal (HPA) axis, with corticosterone well-known as a significant factor in behavioral sensitization development. This study aimed to investigate the effects of Carbetocin (CBT), an analogue of OXT, on the expression of behavioral sensitization to ethanol and concurrent alterations in plasma corticosterone levels in male and female Swiss mice. We also aimed to confirm previous studies on OXT impact on ethanol consumption in male mice, but with a focus on CBT, using the two-bottle choice model and drinking in the dark (DID) methodology. For the sensitization study, mice received either ethanol (1.8 g/kg, ip) or saline treatments daily for 15 consecutive days, followed by treatment with carbetocin (0.64 mg/kg, ip) or a vehicle for 6 days. Subsequently, on day 22, all animals underwent an ethanol challenge to assess the expression of behavioral sensitization. Plasma corticosterone levels were measured on days 21 and 22. CBT effectively prevented the expression of ethanol-induced behavioral sensitization in both male and female subjects, with no alterations detected in corticosterone levels. In the ethanol consumption study, following an initial phase of ethanol acquisition, mice underwent a 6-day treatment with CBT i.p or saline before being reexposed to ethanol. We also found a reduction in ethanol consumption due to CBT treatment. In conclusion, carbetocin emerges as a promising and effective intervention in mitigating ethanol-induced behavioral sensitization and reducing ethanol intake, highlighting its potential significance in alcohol addiction treatment.

This study examines how the design of museum archaeological boxes and the overall museum image affect behavioral intention. This research used partial least squares-structural equation modeling, indicating a relationship between aesthetics, symbolism, affective museum image, perceived value, and behavioral intention. This study found that symbolism predicted behavioral intention. Moreover, aesthetics, symbolism, and affective museum image affected perceived value, in turn triggering behavioral intention. This indicates theoretical and practical implications for museum products.

This article focuses on developing a continuous authentication system using behavioral biometrics to recognize users accessing computing devices. The user’s distinct behavioral biometric is captured through keystroke dynamics, and reward-based reinforcement learning (RL) ideas are applied to recognize them throughout the session. The suggested system adds an extra layer of security to traditional authentication methods, forming a robust continuous authentication system that can be added to static authentication systems. The methodology involves training a RL model to detect unusual user typing patterns and flag suspicious activity. Each user has an agent trained on their historical data, which is preprocessed and used to create episodes for the agent to learn from. The environment involves fetching observations and randomly corrupting them to learn out-of-order behavior. The observation vector includes both running features and summary features. The re-ward function is binary and minimalistic. The Principal Component Analysis (PCA) model is used to encode the running features, and the Double Deep Q-Network (DDQN) algorithm with a fully connected neural network is used as the policy net. The evaluation achieved an average training accuracy and EER (equal error rate) of 94.7% and 0.0126 and test accuracy and ERR of 81.06% and 0.0323 for all users when the number of encoder features was increased. Therefore, it is concluded that by continuously learning and adapting to changing behavior patterns, this approach can provide more secure and personalized authentication, lowering the possibility of unauthorized access and cyberattacks. Overall, the use of reinforcement learning and behavioral biometrics for continuous authentication has the potential to significantly enhance security in the digital age and are effective in identifying each user.

Understanding the complex relationship between sleep and memory is a major challenge in neuroscience. Many studies on memory consolidation in humans suggest that sleep triggers offline memory processes, resulting in less forgetting of declarative memory and performance stabilization in non-declarative memory. However, issues related to non-optimal experimental designs, task characteristics and measurements, and inappropriate data analysis practices can significantly affect the interpretation of the effect of sleep on memory. In this article, we discuss these issues and suggest constructive solutions to address them. We believe that implementing these solutions in future sleep and memory research will significantly advance this field by improving the understanding of the specific role of sleep in memory consolidation.

Cognitive scientists have paid very little attention to magic as a distinctly human activity capable of creating situations or events that are considered impossible because they violate expectations and conclude with the apparent transgression of well-established cognitive and natural laws. And even though magic techniques appeal to all known cognitive processes from sensing, attention and perception to memory and decision making, the relation between science and magic has so far been mostly unidirectional, with the primary goal of unraveling how magic works. Building up from the deconstruction of a classic magic trick, we provide here a cognitive foundation for the use of magic as a unique and largely untapped research tool to dissect cognitive processes in tasks arguably more natural than those usually exploited in artificial laboratory settings. Magicians can submerge every spectator into the precise experimental protocol they have previously designed, accounting with ease for both circumstantial and social contexts. Magicians do not base the success of their experiments in statistical measures that smear out the individual in favor of an average spectator that we know never exists in the real world. They target each and everyone in the audience and, often, with a complete accomplishment. Magicians deliver their cognitive manipulations in real-time, in tight closed-loop with the audience, and in a single trial (they cannot afford to repeat the trick if it fails). Magic has also an inherent and strong social component, merging the private cognitive processes of each spectator with the group dynamics. Finally, when combined with the wide range of precise measuring and wearable technologies available today, magic paves the way for a road not taken towards real-world cognitive science. We dare to speculate that some of the mysteries of how the brain works may be trapped in the split realities present in each magic effect.

Localizing the source of a signal is often as important as deciphering the signal’s message. Localization mechanisms must cope with the challenges of representing the spatial information of weak, noisy signals. Comparing these strategies across modalities and model systems allows a broader understanding of the general principles shaping spatial processing. In this review we focus on the electrosensory system of knifefish and provide an overview of our current understanding of spatial processing in this system, in particular, localization of conspecific signals. We argue that many mechanisms observed in other sensory systems, such as the visual or auditory systems, have comparable implementations in the electrosensory system. Our review therefore describes a field of research with unique opportunities to provide new insights into the principles underlying spatial processing.

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<.001). However, the rate was significantly higher only for borderline PD diagnosis (28.3% vs 6.1% P<.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

Physical activity (PA) is a modifiable factor that may have an influence on the course of Parkinson’s disease (PD). This study aimed to apply a simple behavioral intervention to encourage PD sufferers to increase their everyday physical activity and assess which parameters of motor functions will be improved. The research covered 50 PD patients (28 men and 22 women) aged 40-81 years (65.38 ± 9.23), with a duration of the disease 2-4 years, in stages 1-3 on the Hoehn and Yahr scale. The patients were randomly divided into two groups: the experimental group with behavioral therapy, and the control group without intervention. During 12 weeks the patients from the experimental group had five phone conversations. Each conversation lasted 15 minutes and was an interview about the subjects’ physical activity in the last month. The results were assessed by the Timed Up and Go test (TUG), Unified Parkinson's Disease Rating Scale (UPDRS) – part III, FIR (Functional Index “Repty” – own modification of Functional Independence Measure (FIM)), Functional Ambulation Category (FAC) and International Physical Activity Questionnaire (IPAQ). The results showed that spontaneous physical activity increased in the experimental group and motor functions improved. Physical activity improvement depended on age, body mass index, and gender.

To detect aberrant human behaviors from large volume of passive data collected by smartphones in real time, we propose an online anomaly detection method using Hotelling’s T-squared test. The test statistic is a weighted average, with more weight on the between-individual component when there are little data available for the individual and more weight on the within-individual component when the data are adequate. The algorithm takes only O(1) run time in each update and the required memory usage is fixed after a pre-specified number of updates. The performance of the proposed method, in terms of accuracy, sensitivity and specificity, is consistently better than or equal to the offline method that it builds upon depending on the sample size of the individual data.

Behavioral instability is a new concept used for indicating environmental stress based on behavioral traits. This study investigates the possibility of using behavioral instability as a tool for assessing personality in captive animals. The understanding of personality in captive animals can be a resourceful tool in the development of enrichment programs in order to improve animal welfare. In this study it is examined how an olfactory stimulus affects the behavior of two individuals of the species Ursus maritimus in captivity. When using continuous focal sampling throughout the day it was for many behaviors found that the individuals responded differently to stimuli, indicating that there was a difference in personality. This is shown using multiple approaches. One approach used traditional methods for behavioral analyses and the other approach used the concept of behavioral instability as a new quantitative method. This study proves use of behavioral instability as a new quantitative method for investigating personality, expanding the possibility of comparing personality between species. Moreover, it is shown that outliers, which cause asymmetric distributions, should not be removed in behavioral analysis without careful consideration.

Pain is a multifaceted multisystem disorder that adversely affects neuro-psychological processes. This study compares the effectiveness of central-stimulation (tDCS) and peripheral-stimulation (TENS) in pain-inhibition during a cognitive-task in healthy volunteers and to observe potential neuro-cognitive improvements. Healthy eighty volunteers went through a complete experimental protocol comprising pain-induction (CPT), administration of tDCS/TENS, EEG-data acquisition, and cognitive assessments. The protocol for this study is categorized into 04-groups: G1(Control), G2(TENS), G3(Anodal-tDCS), and G4(Cathodal-tDCS). Paired t-tests (p

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.

Brain-stimulation reward, also known as intracranial self-stimulation (ICSS), is a commonly used procedure for studying brain reward function and drug reward. In electrical ICSS, an electrode is surgically implanted into the medial forebrain bundle in the lateral hypothalamus or the ventral tegmental area in the midbrain. Operant lever responding leads to the delivery of electrical pulse stimulation. The alteration in the stimulation frequency-lever response curve is used to evaluate the impact of pharmacological agents on brain reward function. If a test drug induces a leftward or upward shift in the ICSS response curve, it implies a reward-enhancing or abuse-like effect. Conversely, if a drug causes a rightward or downward shift in the functional response curve, it suggests a reward-attenuating or aversive effect. A significant drawback of electrical ICSS is the lack of cellular selectivity in understanding the neural substrates underlying drug reward versus aversion. Excitingly, recent advancements in optical ICSS (oICSS) have facilitated the development of at least three cell type-specific oICSS models – dopamine-, glutamate-, and GABA-dependent oICSS. In these new models, a comparable frequency-rate response curve has been established and employed to study the substrate-specific mechanisms underlying brain reward function and a drug's rewarding versus aversive effects. In this review article, we summarize recent progress in this exciting research area. The findings in these new behavioral models have not only increased our understanding of the neural mechanisms underlying drug reward and addiction but have also introduced a novel experimental approach in preclinical medication development for treating substance use disorders.

Background: Retinal diseases such as neovascular age related macular degeneration (nAMD), diabetic macular edema (DME) or branch-/central retinal vein occlusion (B/CRVO) have significant implications for patients' social and psychological well-being. To gain a comprehensive understanding of patients' backgrounds and attitudes, we developed an exploratory questionnaire, the Basic Care and Patient Satisfaction Questionnaire (BPZ-9). Methods: The ALBATROS study aimed to assess the care situation of treatment-naïve patients diagnosed with either nAMD, DME or B/CRVO. The data collection took place at the beginning of treatment and after twelve months of anti-VEGF (vascular endothelial growth factor) therapy. The BPZ-9 instrument comprises nine questions to evaluate patients’ psychological and social situation and their satisfaction with treatment. Results: Data were collected from 1.478 nAMD (mean 78 years), 445 DME (67 years), 233 BRVO (70 years) and 144 CRVO (71 years) patients at 102 study centers throughout Germany. Approximately one third of the patients was living alone and six percent were in organized care. One in four patients had difficulties to walk and one in five needed accompany for treatment. Anxiety to lose vision was present in three out of four patients at the beginning and slightly decreased to two out of three over the 12-month treatment preriod. The distress of having a retinal disease was generally higher than the distress related to treatment. Most patients reported high treatment satisfaction (73%) and felt well informed (81%). Conclusion: Patients receiving anti-VEGF therapy commonly experience impaired mobility, dependency on others, distress and the fear of vision loss.

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a rare neurodevelopmental disease caused by mutations in the X-linked CDKL5 gene. CDD is characterized by a broad spectrum of clinical manifestations, including early-onset refractory epileptic seizures, intellectual disability, hypotonia, visual disturbances, and autism-like features. The Cdkl5 knockout (KO) mouse recapitulates several features of CDD, including autistic-like behavior, impaired learning and memory, and motor stereotypies. These behavioral alterations are accompanied by diminished neuronal maturation and survival, reduced dendritic branching and spine maturation, and marked microglia activation. There is currently no cure or effective treatment to ameliorate the symptoms of the disease. Aerobic exercise is known to exert multiple beneficial effects in the brain, not only by increasing neurogenesis, but also by improving motor and cognitive tasks. To date, no studies have analyzed the effect of physical exercise on the phenotype of a CDD mouse model. In view of the positive effects of voluntary running on the brain of mouse models of various human neurodevelopmental disorders, we sought to determine whether voluntary daily running, sustained over a month, could improve brain development and behavioral defects in Cdkl5 KO mice. Our study showed that long-term voluntary running improved hyperlocomotion and impulsivity behaviors, and memory performance of Cdkl5 KO mice. This is correlated with increased hippocampal neurogenesis, neuronal survival, spine maturation, and inhibition of microglia activation. These behavioral and structural improvements were associated with increased BDNF levels. Given the positive effects of BDNF on brain development and function, the present findings support the positive benefits of exercise as an adjuvant therapy for CDD.

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.

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.

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.