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Objective: Alcohol Use Disorder (AUD) is a common, chronically relapsing condition with substantial health and economic costs. United States federal agencies have put out calls in the last decade to expand the scientific evidence base for broad biopsychosocial recovery from AUD and other substance use disorders (SUD). The present study examined the role of physical activity and exercise in early recovery from AUD, with specific attention to changes in brain-derived neurotrophic factor (BDNF) as a marker of neuroplasticity and a potential mechanism for instantiation of recovery-aligned behaviors. Method: Individuals in the first year of recovery from AUD were recruited into a 12-week study with exercise sessions and pre/post-exercise blood sample collection performed in a laboratory setting at baseline, 6 weeks, and 12 weeks. Data analyses included BDNF enzyme-linked immunosorbent assays (ELISA) to establish pre/post-exercise BDNF concentrations, estimation of the magnitude of the effect of exercise on BDNF, and prospective associations of exercise-induced BDNF change with coping, craving, consumption and mood outcome measures. Results: 26 participants were screened, 22 were eligible, 7 had entered the study, and 6 had provided at least one set of pre/post-exercise blood samples when student research ceased on March 23rd, 2020 due to COVID-19 precautions. Participants with at least one set of pre/post-exercise blood samples demonstrated a statistically significant (p=.014) increase from baseline in BDNF levels after exercise, with a large effect size (Cohen's d=1.519;Hedges' g=1.019 ). The impact of this increase from baseline on subsequent measures of coping, craving, mood, and substance use is unclear due to lack of statistical power. Conclusions: This study is the first to demonstrate that individuals recovering from AUD can increase serum levels of BDNF from baseline levels via sessions of physical exercise. (PsycInfo Database Record (c) 2023 APA, all rights reserved)
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The current outbreak of COVID-19 is caused by the SARS-CoV-2 virus that has affected > 210 countries. Various steps are taken by different countries to tackle the current war-like health situation. In India, the Ministry of AYUSH released a self-care advisory for immunomodulation measures during the COVID-19 and this review article discusses the detailed scientific rationale associated with this advisory. Authors have spotted and presented in-depth insight of advisory in terms of immunomodulatory, antiviral, antibacterial, co-morbidity associated actions, and their probable mechanism of action. Immunomodulatory actions of advised herbs with no significant adverse drug reaction/toxicity strongly support the extension of advisory for COVID-19 prevention, prophylaxis, mitigations, and rehabilitation capacities. This advisory also emphasized Dhyana (meditation) and Yogasanas as a holistic approach in enhancing immunity, mental health, and quality of life. The present review may open-up new meadows for research and can provide better conceptual leads for future researches in immunomodulation, antiviral-development, psychoneuroimmunology, especially for COVID-19.Copyright © 2021, Institute of Korean Medicine, Kyung Hee University.
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The proceedings contain 96 papers. The topics discussed include: practical pharmacotherapy for opioid use disorder in the age of fentanyl;can COVID-19 cause acute psychosis in pediatric patients? a case report;a survey of bullying experiences in a child and adolescent psychiatric clinic population;acute emergence of suicidal thoughts following Lemborexant initiation: an adverse reaction case report;assessing the unmet clinical need and opportunity for digital therapeutic intervention in schizophrenia: perspective from people with schizophrenia;rapid antidepressant effects and MADRS item improvements with AXS-05 (DEXTROMETHORPHAN-BUPROPION), an oral NMDA receptor antagonist in major depressive disorder: results from two randomized double-blind, controlled trials;targeting lncRNA NEAT1 impedes Alzheimers disease progression via MicroRNA-193a mediated CREB/BDNF and NRF2/NQO1 pathways;and impact of AXS-05 (DEXTROMETHORPHAN-BUPROPION), an Oral NMDA receptor antagonist, on Anhedonic symptoms in major depressive disorder.
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Purpose: Disability in knee osteoarthritis (KOA) is known to be largely due to pain, the mechanism of which is complex and multidimensional with alterations in nociceptive processing in the peripheral and central nervous system (CNS) leading to persistent pain. Current clinical practice guidelines for KOA provide strong recommendations for education and exercise including land-based or mind-body approaches. However, individually these strategies are only moderately effective. One potential reason for this is a lack of understanding of their underlying mechanisms and how their combination might impact nervous system modulation. Neuromuscular exercise is known to improve lower extremity strength. Mind-body approaches as well as pain neuroscience education (PNE) are uniquely positioned to potentially reverse CNS adaptations by inducing positive neuroplastic changes and improving descending modulation of pain resulting in decreased pain. To our knowledge, neuromuscular exercise, mind-body techniques, and PNE have not been studied in combination. We therefore aimed to establish the feasibility of an intervention consisting of these three elements referred to as Pain Informed Movement (PIM). The results of this study will inform necessary modifications for a two-arm pilot randomized controlled trial (RCT). Method(s): This study was a single-arm feasibility trial with a nested qualitative component and the primary feasibility outcome of complete follow up. Inclusion criteria: age >= 40 years, KOA clinical diagnosis or people fulfilling the NICE diagnostic criteria, and average pain intensity >=3/10 on the numeric pain rating scale. PIM consisted of twice weekly in-person exercise sessions and a third home exercise session for 8 weeks. In addition, PNE, provided as online videos, covered the following topics: purpose of pain, neurophysiological changes associated with pain, movement guidelines when pain persists, mind-body techniques to impact neurophysiology and support moving with ease that included breath awareness and regulation, muscle tension regulation, awareness of pain related thoughts and emotions, and relaxation. The mind-body techniques and the PNE topics were implemented during the group exercise sessions that included evidence-based neuromuscular exercises aimed at improving sensorimotor control and functionality of the knee joint. Participants completed questionnaires and in-person assessments at baseline and at program completion. Assessments included weight and height, chair stands as a measure of functional leg strength, and conditioned pain modulation to assess efficiency of the descending modulatory pathways. Participants also had their blood drawn to monitor changes in brain derived neurotrophic factor (BDNF), a marker of neuroplasticity. Questionnaires included the Pain Catastrophizing Scale, Hospital Anxiety and Depression Scale, the Knee Injury and Osteoarthritis Outcome Score - function and pain subscales, Chronic Pain Self Efficacy scale, pain intensity rated in the past 24 hours, the past week, and worst pain in the past 24 hours. Secondary feasibility outcomes included acceptability of the intervention, burden of assessments, recruitment rate, compliance rate, adherence rate, and self-reported adverse events. Feasibility findings were evaluated against a-priori success criteria. In the qualitative component, participants were invited to an online focus group and were asked about their experience and perceptions of the program. Interview recordings were analyzed using thematic content analysis to identify suggestions for program modification. Result(s): In total, 19 participants (mean age 63.3 years (SD 10.5), 73% female) were enrolled, with a complete follow up rate of 74% (n=14) for our primary objective, indicating that modifications would be needed to proceed. Of the 5 dropouts, only one was study related. We will be adding additional inclusion criteria of: ability to get up and down from the floor independently, and no use of mobility aids. Adherence to in-person treatment sessions was 91%, hich indicates proceeding with the protocol for the next phase (i.e., pilot RCT). Some absences were due to unmodifiable factors (e.g., COVID-19). We will make protocol amendments for the purpose of improving the adherence rate to include 'no planned absences'. All other success criteria were met: recruitment rate, compliance to exercise sessions, program acceptability, duration, frequency, and delivery, likelihood of recommending the program to others and taking the program again, burden, and adverse events (Table 1). Analysis of the focus groups revealed that the video content pertaining to the mind-body techniques would benefit from on screen demonstrations by the instructor to assist with participants' execution of breath and muscle tension regulation. The majority of participants improved in most of the physical assessment outcomes and questionnaires (Table 2). Conclusion(s): The PIM program is feasible, acceptable, not burdensome, does not cause adverse events, and had an excellent compliance rate. Minor modifications are needed to optimize enrolment and adherence rates. Although improvements in pain, function, and psychological measures were observed, the feasibility nature of this study precludes any conclusions regarding efficacy. A pilot two-arm RCT will be conducted to establish the feasibility and explore potential effects of PIM when compared to conventional neuromuscular exercise and standard OA education. [Formula presented] [Formula presented]Copyright © 2023
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Background: Vitamin D deficiency during pregnancy is associated with a child's neurocognitive development. During the COVID-19 pandemic, the Capute Scales have become ineffective because requiring face-to-face interaction to examine children's neurocognitive development. Brain-Derived Neurotrophic Factor (BDNF) is an alternative method to determine children's neurocognitive development through blood sampling. This study aims to evaluate the relationships between BDNF and the Capute Scales in the offspring of mothers with vitamin D levels. Methods: A diagnostic study from 14 community health centers in Semarang City, Central Java, Indonesia, was conducted. The study was performed from August 2017 until August 2018 and included vitamin D level records at 20–24 weeks of normal gestation in 2017 from all single births at these community health centers. The cases were divided into two groups: 30 children born to mothers with normal vitamin D levels (25(OH)D > 20 ng/mL) and 30 children born to mothers with vitamin D deficiency (25(OH)D < 20 ng/ml). This study aimed to assess the relationship between BDNF levels and the Capute Scales of children aged 2 years and to determine the cut-off value based on each group's examination of BDNF levels. Results: The mean age of pregnant women whose vitamin D levels were checked was 29.32 years. The cut-off value of BDNF among the two groups was 7968 pg/mL. Of the 55 samples that met the Capute Scales criteria, 44 had a BDNF value less than the cut-off value, and 11 samples had a BDNF value more than the cut-off value. Meanwhile, of the five samples that met the Capute Scales criteria and were suspected of mental retardation, three had a BDNF value less than the cut-off value, and two had a BDNF value more than the cut-off value. The sensitivity, specificity, positive, and negative predictive values were 80%, 60%, 0.93, and 0.15, respectively. Conclusions: BDNF levels can be an alternative neurocognitive examination in children born to mothers with normal and deficient vitamin D levels. BDNF is a growth factor that plays an important role in neurons' differentiation, growth, and survival in the postnatal phase. © 2023, Sanglah General Hospital. All rights reserved.
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Comorbidities due to inflammatory bowel disease (IBD) and anxiety are commonly acknowledged; however, their underlying basis is unclear. In the current study, we first conducted a clinical retrospective analysis to identify the enhancive incidence rate of IBD before or after the epidemic of Corona Virus Disease 2019 (COVID-19), with higher Generalized Anxiety Disorder-7 (GAD-7), as well as poorer Gastrointestinal Quality of Life Index (GIQLI). Then, the dextran sodium sulfate (DSS) and chronic unpredictable stress (CUS)-induced IBD and anxiety comorbid models were established with the correlational relations between symptoms of IBD and anxiety-related behaviors. We found dysfunctional up-regulation of a new inflammatory factor interleukin (IL)-19 in the colon of DSS/CUS treated mice. Overexpression of IL-19 in colon induced anxious phenotypes, and accelerated the anxious condition and symptoms of colitis in the DSS/CUS model by promoting the expression of inducible nitric oxide synthase (iNOS), IL-1ß, and IL-6 pro-inflammatory factors, and activating signal transducer and activator of transcription 3 (STAT3) signaling pathway in the colon. Furthermore, overexpression of IL-19 in the colon also reduced the expression levels of brain-derived neurotrophic factor (BDNF), extracellular signal-regulated kinase (ERK), and cAMP-response element binding protein (CREB) signaling pathways activity in the hippocampus. These results suggest that IL-19 was a pivotal player in DSS/CUS-induced comorbidities of colitis and anxiety with different signaling pathways for the colon and hippocampus, which provides a candidate gene to explore the pathophysiology of comorbidities due to colitis and anxiety.
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Anxiety , Colitis , Interleukins , Animals , Mice , Colitis/chemically induced , Colitis/immunology , Dextran Sulfate/adverse effects , Quality of Life , Retrospective StudiesABSTRACT
Furin is an important mammalian proprotein convertase that catalyzes the proteolytic maturation of a variety of prohormones and proproteins in the secretory pathway. In the brain, the substrates of furin include the proproteins of growth factors, receptors and enzymes. Emerging evidence, such as reduced FURIN mRNA expression in the brains of Alzheimer's disease patients or schizophrenia patients, has implicated a crucial role of furin in the pathophysiology of neurodegenerative and neuropsychiatric diseases. Currently, compared to cancer and infectious diseases, the aberrant expression of furin and its pharmaceutical potentials in neurological diseases remain poorly understood. In this article, we provide an overview on the physiological roles of furin and its substrates in the brain, summarize the deregulation of furin expression and its effects in neurodegenerative and neuropsychiatric disorders, and discuss the implications and current approaches that target furin for therapeutic interventions. This review may expedite future studies to clarify the molecular mechanisms of furin deregulation and involvement in the pathogenesis of neurodegenerative and neuropsychiatric diseases, and to develop new diagnosis and treatment strategies for these diseases.
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Furin , Neurodegenerative Diseases , Animals , Furin/genetics , Furin/physiology , Humans , Proprotein Convertases/geneticsABSTRACT
Donepezil hydrochloride is an acetylcholine esterase inhibitor studied and approved to treat Alzheimer’s disease (AD). However, this drug can have positive therapeutic potential in treating different conditions, including various neurodegenerative disorders such as other types of dementia, multiple sclerosis, Parkinson’s disease, psychiatric and mood disorders, and even infectious diseases. Hence, this study reviewed the therapeutic potential of this drug in treating Alzheimer’s and other diseases by reviewing the articles from databases including Web of Science, Scopus, PubMed, Cochrane, and Science Direct. It was shown that donepezil could affect the pathophysiology of these diseases via mechanisms such as increasing the concentration of acetylcholine, modulating local and systemic inflammatory processes, affecting acetylcholine receptors like nicotinic and muscarinic receptors, and activating various cellular signaling via receptors like sigma-1 receptors. Despite many therapeutic potentials, this drug has not yet been approved for treating non-Alzheimer’s diseases, and more comprehensive studies are needed.
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Introduction: Adolescents' cognitive performance is impacted by factors such as sleep habits, chronotypes and also genetic characteristics. The periods of human sleep and wakefulness are controlled by homeostatic and circadian factors, which the combination generates variations in the preferences for hours of activity and rest, called chronotypes. Chronotypic classification impacts cognitive skills such as logic and problem solving. In adolescence, there is a greater tendency to evening chronotype. The neural factor called BDNF, Brain- Derived Neurotrophic Factor, showed a significant role in cognitive performance variations as in different sleep patterns. The human BDNF gene has a frequent polymorphism called Val66Met, related to several cognitive functions and different patterns of sleep and circadian rhythm. Objective: Evaluate the association of BDNF Val66Met polymorphism with circadian patterns and cognitive performance on tests of attention, in high school students. Methods: High school students, aged between 15 and 17 years old were included in the study, whose cognitive attention skills were investigated by the Psychological Battery for Assessment of Attention. Their BDNF genotypes were determined by analyzing self-collected oral cell samples, which were amplified by real-time PCR using fluorescent probes. Chronotypic characteristics were evaluated by completing two morningness and eveningness scales. Because of the pandemic of COVID-19, a questionnaire about the presence of symptoms, in the previous days of the tests, was included. At present, volunteers are being evaluated through actigraphy. Results: Eighty-five adolescents were evaluated in that study. The average attention score of students who study in the afternoon was lower than individuals who study in the morning. The average score attention for the female gender was significantly lower than that obtained for the male gender. The students who reported symptoms of COVID- 19 had a significantly lower attention score. Lastly, there was no correlation between the chronotype defined by the scales, the performance in the attention test, or even the BDNF genotype of the participants. Conclusion: The central findings obtained, in the first phase of the study, complement the understanding of the associations between the parameters of cognition, chronobiology and genetic aspects. In the next phase, the use of actigraphy will make it possible to deepen these analyzes and conclusions.
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Enabling challenging applications of nanomedicine and precision medicine in the treatment of neurodegenerative disorders requires deeper investigations of nanocarrier-mediated biomolecular delivery for neuronal targeting and recovery. The successful use of macromolecular biotherapeutics (recombinant growth factors, antibodies, enzymes, synthetic peptides, cell-penetrating peptide-drug conjugates, and RNAi sequences) in clinical developments for neuronal regeneration should benefit from the recent strategies for enhancement of their bioavailability. We highlight the advances in the development of nanoscale materials for drug delivery in neurodegenerative disorders. The emphasis is placed on nanoformulations for the delivery of brain-derived neurotrophic factor (BDNF) using different types of lipidic nanocarriers (liposomes, liquid crystalline or solid lipid nanoparticles) and polymer-based scaffolds, nanofibers and hydrogels. Self-assembled soft-matter nanoscale materials show favorable neuroprotective characteristics, safety, and efficacy profiles in drug delivery to the central and peripheral nervous systems. The advances summarized here indicate that neuroprotective biomolecule-loaded nanoparticles and injectable hydrogels can improve neuronal survival and reduce tissue injury. Certain recently reported neuronal dysfunctions in long-COVID-19 survivors represent early manifestations of neurodegenerative pathologies. Therefore, BDNF delivery systems may also help in prospective studies on recovery from long-term COVID-19 neurological complications and be considered as promising systems for personalized treatment of neuronal dysfunctions and prevention or retarding of neurodegenerative disorders.
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In the form of a literary review, this work set itself the task of examining the professional literature published on this topic and selecting representative literary sources that document the interdisciplinary nature of this scientific discipline. Do této kategorie spadá mimo jiné publikace Ratio of serum pro BDNF to BDNF and its association with cognitive performance and brain morphometry in mild cognitive impairment, autorů Čechová a kol. (2020) Gray matter atrophy, but not vascular brain injury is related to cognitive impairment in patients with heart failure, článek Comparison of brain atrophy and cognitive performance in individuals with low and high cardiovascular riskautorů Restrepo a kol. (2020) publikovali v časopise Archives of clinical neuropsychology: the official journal of the National Academy of Neuropsychologists studii s názvem Return on Investment and Value Research in Neuropsychology: A Call to Arms.
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Background & Aims: Beginning in 2020, a deadly disease called COVID-19 spread throughout the world, plunging all countries into a viral infection. Viral infections are naturally associated with upper respiratory tract infections, which are commonly reported with fever, headache, and cough. COVID-19 virus can infect a person's respiratory system and lungs, eventually leading to death. The virus can first activate and infect macrophages. Macrophages then transfer COVID 19 to T cells and make them weak. In addition, by weakening T cells, T cell subsets are activated to increase cytokines to enhance the immune response. T cells, CD4 + T cells and CD8 + T cells play an important antiviral role in the body. It is noteworthy that CD4 + T cells in the body produce T cell-dependent (B) cells to increase virus-specific antibodies. On the other hand, CD8 + T cells are a toxic cell and can kill virus-infected cells. Most published studies have focused on the effect of aerobic exercise on immune system function. Recent studies have shown that tai chi and yoga exercises can also be beneficial for immune system function. Exercise has long been known as an important modulator of inflammatory processes. Exercise can apparently have both tonic and suppressive effects on the immune system. The effect of exercise on innate and acquired safety parameters depends on the intensity, load and duration of exercise. As the severity increases, immune function and ultimately the risk of infection increase. These risks depend on immune system regulators (genetics, nutritional status, psychological stress, circadian rhythms), environmental stressors (extreme temperatures, airway irritants) that increase inflammation. In response to exercise, immune cells grow, proliferate, and produce molecules such as cytokines and cytotoxic granules. Prolonged exercise, at least in healthy individuals, appears to reduce basal inflammatory status by reducing the circulation of inflammatory cytokines. Regular periods of short-term training (i.e., up to 45 minutes) with moderate intensity boost the immune system (increase T cells) while frequent periods of long-term high-intensity training (> 2 hours) can suppress the immune system. Acute exercise, even in healthy individuals, leads to a strong inflammatory response that is mediated by leukocyte mobilization (even for short periods of 6 minutes) and increases potent inflammatory mediators such as TNF-a, IL-1. The effect of increasing aerobic capacity on improving lung function and preventing lung injury can be summarized in four mechanisms. The first mechanism of aerobic exercise can prevent the suppression of the immune system by affecting the immune system and increase anti-inflammatory factors. The second mechanism contains the role of aerobic capacity in restoring the elasticity of lung tissue to normal and increasing the strength and endurance of the respiratory muscles, which helps increase ventilation, and reduce lung damage. The third mechanism includes the role of aerobic capacity as an antioxidant to limit the production of free radicals and oxidative damage. The fourth mechanism involves the role of aerobic capacity in reducing cough and clearing the airways by improving pulmonary safety and autonomic modulation.
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A growing body of evidence clearly indicates the beneficial effects of physical activity (PA) on cognition. The importance of PA is now being reevaluated due to the increase in sedentary behavior in older adults during the COVID-19 pandemic. Although many studies in humans have revealed that PA helps to preserve brain health, the underlying mechanisms have not yet been fully elucidated. In this review, which mainly focuses on studies in humans, we comprehensively summarize the mechanisms underlying the beneficial effects of PA or exercise on brain health, particularly cognition. The most intensively studied mechanisms of the beneficial effects of PA involve an increase in brain-derived neurotrophic factor (BDNF) and preservation of brain volume, especially that of the hippocampus. Nonetheless, the mutual associations between these two factors remain unclear. For example, although BDNF presumably affects brain volume by inhibiting neuronal death and/or increasing neurogenesis, human data on this issue are scarce. It also remains to be determined whether PA modulates amyloid and tau metabolism. However, recent advances in blood-based biomarkers are expected to help elucidate the beneficial effects of PA on the brain. Clinical data suggest that PA functionally modulates cognition independently of neurodegeneration, and the mechanisms involved include modulation of functional connectivity, neuronal compensation, neuronal resource allocation, and neuronal efficiency. However, these mechanisms are as yet not fully understood. A clear understanding of the mechanisms involved could help motivate inactive persons to change their behavior. More accumulation of evidence in this field is awaited.
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With the current national opioid crisis, it is critical to examine the mechanisms underlying pathophysiologic interactions between human immunodeficiency virus (HIV) and opioids in the central nervous system (CNS). Recent advances in experimental models, methodology, and our understanding of disease processes at the molecular and cellular levels reveal opioid-HIV interactions with increasing clarity. However, despite the substantial new insight, the unique impact of opioids on the severity, progression, and prognosis of neuroHIV and HIV-associated neurocognitive disorders (HAND) are not fully understood. In this review, we explore, in detail, what is currently known about mechanisms underlying opioid interactions with HIV, with emphasis on individual HIV-1-expressed gene products at the molecular, cellular and systems levels. Furthermore, we review preclinical and clinical studies with a focus on key considerations when addressing questions of whether opioid-HIV interactive pathogenesis results in unique structural or functional deficits not seen with either disease alone. These considerations include, understanding the combined consequences of HIV-1 genetic variants, host variants, and µ-opioid receptor (MOR) and HIV chemokine co-receptor interactions on the comorbidity. Lastly, we present topics that need to be considered in the future to better understand the unique contributions of opioids to the pathophysiology of neuroHIV. Graphical Abstract Blood-brain barrier and the neurovascular unit. With HIV and opiate co-exposure (represented below the dotted line), there is breakdown of tight junction proteins and increased leakage of paracellular compounds into the brain. Despite this, opiate exposure selectively increases the expression of some efflux transporters, thereby restricting brain penetration of specific drugs.
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AIDS Dementia Complex/complications , COVID-19 , HIV Infections/complications , Opioid Epidemic , Opioid-Related Disorders/epidemiology , HIV-1/immunology , HumansABSTRACT
Despite the hard times COVID-19 has imposed on us, the Biomedical Journal strives to provide fresh and compelling reading material - to be enjoyed safely from home. In this issue, we glance behind the scenes of dental stem cell preservation for potential therapeutic use, and discover that cancer cells hijack podoplanin expression to induce thrombosis. Moreover, we learn how the helicase DDX17 promotes tumour stemness, how genetic defects in meiosis and DNA repair cause premature ovarian insufficiency, and that the brain-derived neurotrophic factor is associated with several psychiatric diseases. Further accounts relate the role of miR-95-3p in colorectal cancer, the protective power of eggplants against mercury poisoning, and the predictive value of inhibin A for premature delivery. Finally, the very rare case of adenoid cystic carcinoma in the external auditory canal receives some attention, and we get to read up on how 3D imaging and modelling combines functional and aesthetic repair of cleft lip and palate cases.