Mini-heterochromatin domains constrain the cis-regulatory impact of SVA transposons in human brain development and disease.

SVA (SINE (short interspersed nuclear element)-VNTR (variable number of tandem repeats)-Alu) retrotransposons remain active in humans and contribute to individual genetic variation. Polymorphic SVA alleles harbor gene regulatory potential and can cause genetic disease. However, how SVA insertions are controlled and functionally impact human disease is unknown. Here we dissect the epigenetic regulation and influence of SVAs in cellular models of X-linked dystonia parkinsonism (XDP), a neurodegenerative disorder caused by an SVA insertion at the TAF1 locus. We demonstrate that the KRAB zinc finger protein ZNF91 establishes H3K9me3 and DNA methylation over SVAs, including polymorphic alleles, in human neural progenitor cells. The resulting mini-heterochromatin domains attenuate the cis-regulatory impact of SVAs. This is critical for XDP pathology; removal of local heterochromatin severely aggravates the XDP molecular phenotype, resulting in increased TAF1 intron retention and reduced expression. Our results provide unique mechanistic insights into how human polymorphic transposon insertions are recognized and how their regulatory impact is constrained by an innate epigenetic defense system.

LINE-1 retrotransposons drive human neuronal transcriptome complexity and functional diversification.

The genetic mechanisms underlying the expansion in size and complexity of the human brain remain poorly understood. Long interspersed nuclear element-1 (L1) retrotransposons are a source of divergent genetic information in hominoid genomes, but their importance in physiological functions and their contribution to human brain evolution are largely unknown. Using multiomics profiling, we here demonstrate that L1 promoters are dynamically active in the developing and the adult human brain. L1s generate hundreds of developmentally regulated and cell type-specific transcripts, many that are co-opted as chimeric transcripts or regulatory RNAs. One L1-derived long noncoding RNA, LINC01876, is a human-specific transcript expressed exclusively during brain development. CRISPR interference silencing of LINC01876 results in reduced size of cerebral organoids and premature differentiation of neural progenitors, implicating L1s in human-specific developmental processes. In summary, our results demonstrate that L1-derived transcripts provide a previously undescribed layer of primate- and human-specific transcriptome complexity that contributes to the functional diversification of the human brain.

HPV self-sampling versus healthcare provider collection on the effect of cervical cancer screening uptake and costs in LMIC: a systematic review and meta-analysis.

BACKGROUND: Cervical cancer is a major global health issue, with 89% of cases occurring in low- and middle-income countries (LMICs). Human papillomavirus (HPV) self-sampling tests have been suggested as an innovative way to improve cervical cancer screening uptake and reduce the burden of disease. The objective of this review was to examine the effect of HPV self-sampling on screening uptake compared to any healthcare provider sampling in LMICs. The secondary objective was to estimate the associated costs of the various screening methods. METHOD: Studies were retrieved from PubMed, Embase, CINAHL, CENTRAL (by Cochrane), Web of Science, and ClinicalTrials.gov up until April 14, 2022, and a total of six trials were included in the review. Meta-analyses were performed mainly using the inverse variance method, by pooling effect estimates of the proportion of women who accepted the screening method offered. Subgroup analyses were done comparing low- and middle-income countries, as well as low- and high-risk bias studies. Heterogeneity of the data was assessed using I2. Cost data was collected for analysis from articles and correspondence with authors. RESULTS: We found a small but significant difference in screening uptake in our primary analysis: RR 1.11 (95% CI: 1.10-1.11; I2 = 97%; 6 trials; 29,018 participants). Our sensitivity analysis, which excluded one trial that measured screening uptake differently than the other trials, resulted in a clearer effect in screening uptake: RR: 1.82 (95% CI: 1.67-1.99; I2 = 42%; 5 trials; 9590 participants). Two trials reported costs; thus, it was not possible to make a direct comparison of costs. One found self-sampling more cost-effective than the provider-required visual inspection with acetic acid method, despite the test and running costs being higher for HPV self-sampling. CONCLUSION: Our review indicates that self-sampling improves screening uptake, particularly in low-income countries; however, to this date, there remain few trials and associated cost data. We recommend further studies with proper cost data be conducted to guide the incorporation of HPV self-sampling into national cervical cancer screening guidelines in low- and middle-income countries. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020218504.

CRISPRi-mediated transcriptional silencing in iPSCs for the study of human brain development.

This protocol describes the design and use of CRISPRi-mediated transcriptional silencing in human iPSCs, for loss-of-function studies in brain development research. The protocol avoids single cell selection, thereby eliminating side effects of clonal expansion and sites of viral integration. We also describe a neural progenitor differentiation protocol and discuss the challenges of target-specific lentiviral silencing, efficient silencing levels, and off-target effects. For complete details on the use and execution of this protocol, please refer to Johansson et al. (2022).

SLEEP: intervention with weighted blankets for children with attention deficit hyperactivity disorder (ADHD) and sleep problems: study protocol for a randomised control trial.

INTRODUCTION AND OBJECTIVES: Children with attention deficit hyperactivity disorder (ADHD) have an increased risk of sleep problems. Weighted blankets are one possible non-pharmacological intervention for these problems in this group of children. However, the effectiveness of weighted blankets is insufficiently investigated. This study aims to investigate the effectiveness of weighted blankets in terms of sleep, health-related outcomes and cost-effectiveness as well as to explore children's and parents' experiences of a sleep intervention with weighted blankets. METHODS AND ANALYSIS: This study is a randomised placebo-controlled crossover trial comparing the effect of weighted fibre blankets (active) with fibre blankets without weight (control). Children aged 6-13 years, recently diagnosed with uncomplicated ADHD with verified sleep problems, were included in the study. The study period is 4 weeks for each condition, respectively, and then an 8-week follow-up. A total of 100 children diagnosed with ADHD and sleep problems will enter the study. The primary outcomes are sleep and cost per quality-adjusted life years. The secondary outcomes are health-related quality of life, ADHD symptoms, psychological distress and anxiety. Interviews with a subsample of the participating children and parents will be conducted for exploring the experiences of the intervention. ETHICS AND DISSEMINATION: Ethical approval of the trial has been obtained from the Swedish Ethical Review Authority (number 2019--2158) and conforms to the principles outlined in the Declaration of Helsinki (WMA, 2013). Results will be reported as presentations at peer-review conferences, in articles in peer-review journals and meetings with healthcare providers. TRIAL REGISTRATION NUMBER: NCT04180189.

A cis-acting structural variation at the ZNF558 locus controls a gene regulatory network in human brain development.

The human forebrain has expanded in size and complexity compared to chimpanzees despite limited changes in protein-coding genes, suggesting that gene expression regulation is an important driver of brain evolution. Here, we identify a KRAB-ZFP transcription factor, ZNF558, that is expressed in human but not chimpanzee forebrain neural progenitor cells. ZNF558 evolved as a suppressor of LINE-1 transposons but has been co-opted to regulate a single target, the mitophagy gene SPATA18. ZNF558 plays a role in mitochondrial homeostasis, and loss-of-function experiments in cerebral organoids suggests that ZNF558 influences developmental timing during early human brain development. Expression of ZNF558 is controlled by the size of a variable number tandem repeat that is longer in chimpanzees compared to humans, and variable in the human population. Thus, this work provides mechanistic insight into how a cis-acting structural variation establishes a regulatory network that affects human brain evolution.

Bacterial colonisation during regular daily use of a power-driven water flosser and risk for cross-contamination. Can it be prevented?

OBJECTIVE: To assess whether bacterial colonisation in a power-driven water flosser can be prevented. MATERIALS AND METHODS: Twenty-four patients undergoing supportive periodontal treatment used 2 power-driven water flossers [Sonicare AirFloss (SAF), AirFloss Ultra (SAFU)] for 12 weeks each as follows: (a) with bottled water (BW); (b) with BW and cleaning the device extra-orally twice per week with chlorhexidine gluconate or (c) essential-oil-based (EO) mouth-rinse; (d) with EO only. Water-jet samples were taken after 6 and 12 weeks with the used nozzle and after exchanging to a brand-new nozzle. After 12 weeks, all devices underwent an intensive cleaning procedure. Samples were analysed by PCR-based method for cariogenic and periodontal pathogens and culture for staphylococci, aerobe gram-negative bacteria, and Candida sp. RESULTS: Contamination of SAF/SAFU with Streptococcus mutans was found in > 95% of the samples; periodontal pathogens and aerobe gram-negative bacteria were detected in 19-56% of the samples, while Staphylococcus aureus and Candida sp. were identified only in few samples. Contamination rate was basically unaffected by time-point, device, or way of use. Further, exchanging the nozzle did not prevent transmission of a contaminated water-jet, but the intensive cleaning reduced most of the pathogens significantly, except of S. mutans. CONCLUSION: Neither a specific way of use nor exchanging the nozzle prevented bacterial colonisation and transmission of biofilm components via the water-jet of SAF/SAFU. CLINICAL RELEVANCE: Bacterial colonisation in a power-driven water flosser seems impossible to prevent; to restrict the risk of cross-contamination within a household, one device per person should be recommended.

Distinct subcellular autophagy impairments in induced neurons from patients with Huntington's disease.

Huntington's disease is a neurodegenerative disorder caused by CAG expansions in the huntingtin (HTT) gene. Modelling Huntington's disease is challenging, as rodent and cellular models poorly recapitulate the disease as seen in ageing humans. To address this, we generated induced neurons through direct reprogramming of human skin fibroblasts, which retain age-dependent epigenetic characteristics. Huntington's disease induced neurons (HD-iNs) displayed profound deficits in autophagy, characterized by reduced transport of late autophagic structures from the neurites to the soma. These neurite-specific alterations in autophagy resulted in shorter, thinner and fewer neurites specifically in HD-iNs. CRISPRi-mediated silencing of HTT did not rescue this phenotype but rather resulted in additional autophagy alterations in control induced neurons, highlighting the importance of wild-type HTT in normal neuronal autophagy. In summary, our work identifies a distinct subcellular autophagy impairment in adult patient derived Huntington's disease neurons and provides a new rationale for future development of autophagy activation therapies.

Empowerment-Based Physical Activity Intervention for People with Advanced Dry Age-Related Macular Degeneration: Mixed-Methods Protocol.

Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment and impacts daily life. These impacts include loss of social activities, decreased functional independence, and reduced physical activity. This protocol aims to describe a prospective, mixed-methodology for studying a population with AMD before, during, and after an empowerment-based physical activity intervention (EPI). A study framework was also developed for EPI. The intervention will include 20 older individuals (age 65+ years) with AMD recruited in Sweden. The intervention period is six months and comprises adapted physical activity and social activities in a group twice a week and individual health coaching on three occasions. The quantitative pre-test and three follow-ups include physical functional tests, an accelerometer that monitors physical activity continuously for one week, and questionnaires. Individual and focus-group interviews and ethnographic observations will explore the experience of living with AMD and what it means to participate in the EPI for individuals with AMD. The chosen methodology offers a structured way for researchers to explore the experiences and factors that may provide insights into the potential of creative supervised, adapted physical activity in groups, health coaching, and socialising that are significant to enable well-being among older individuals with AMD.

Patients' opinion on the use of 2 generations of power-driven water flossers and their impact on gingival inflammation.

OBJECTIVES: To assess patients' opinion on the use of 2 generations of power-driven water flossers and their impact on gingival inflammation. MATERIAL & METHODS: In the present prospective cohort study 24 periodontitis patients under regular supportive periodontal therapy used daily 2 generations of a power-driven water flosser (Sonicare AirFloss [SAF] and Sonicare AirFloss Ultra [SAFU]) for 12 weeks each. Patients were instructed to position the nozzle interproximally from the buccal aspect at each interproximal space. Patients' opinion was assessed by a questionnaire and interproximal bleeding on probing (BoP) was recorded. RESULTS: Overall satisfaction with SAF/SAFU was rated high, by about 80% of the patients. About 66% of the patients preferred SAF/SAFU compared to their previous interdental cleaning device and indicated that they would continue using SAF/SAFU after the study; none of the patients reported any discomfort or pain. Compared to only tooth brushing, daily use of SAF/SAFU caused a significant reduction of interproximal BoP values, which were well maintained over 6 months; that is, BoP at interproximal buccal and oral sites (pooled), as well as at interproximal buccal and oral sites separately, was proportionately reduced by 29.1%, 41.2%, and 24.8%, respectively (pooled: p = 0.027; buccal sites: p = 0.030; oral sites: p = 0.030). CONCLUSION: Patients were very fond of the power-driven water flossers tested herein, and daily use of the devices for 6 months (i.e., each device was used for 3 months) resulted in a significant reduction of gingival inflammation interproximally.

Bacterial colonization of a power-driven water flosser during regular use. A proof-of-principle study.

OBJECTIVES: The present proof-of-principle study assessed whether daily use of a power-driven water flosser (Sonicare AirFloss; SAF) leads to bacterial colonization in the nozzle and/or the device, resulting in contaminated water-jet. MATERIAL AND METHODS: In five participants, saliva samples at baseline and water-jet samples of devices used daily with bottled water for 3 weeks (test) were collected. Additionally, water-jet samples from devices used daily with bottled water extra-orally for 3 weeks (positive control) and from brand new devices (negative control), as well as samples from newly opened and 1- and 3-week opened water bottles were collected. Colony forming units (CFU) were recorded after 48 h culturing and 20 oral pathogens were assessed by polymerase chain reaction-based analysis. RESULTS: Distinct inter-individual differences regarding the number of detected bacteria were observed; water-jet samples of test devices included both aerobic and anaerobic bacterial species, with some similarities to the saliva sample of the user. Water-jet samples from positive control devices showed limited number of aerobic and anaerobic bacterial species, while the samples from negative control devices did not show any bacterial species. Very few aerobic bacteria were detected only in the 3-week-old bottled water samples, while samples of newly and 1-week opened water bottles did not show any bacterial growth. CONCLUSIONS: The present proof-of-principle study showed that daily use of a power-driven water flosser for 3 weeks resulted in bacterial colonization in the nozzle and/or device with both aerobic and anaerobic, not only oral, species, that are transmitted via the water-jet.

Activation of endogenous retroviruses during brain development causes an inflammatory response.

Endogenous retroviruses (ERVs) make up a large fraction of mammalian genomes and are thought to contribute to human disease, including brain disorders. In the brain, aberrant activation of ERVs is a potential trigger for an inflammatory response, but mechanistic insight into this phenomenon remains lacking. Using CRISPR/Cas9-based gene disruption of the epigenetic co-repressor protein Trim28, we found a dynamic H3K9me3-dependent regulation of ERVs in proliferating neural progenitor cells (NPCs), but not in adult neurons. In vivo deletion of Trim28 in cortical NPCs during mouse brain development resulted in viable offspring expressing high levels of ERVs in excitatory neurons in the adult brain. Neuronal ERV expression was linked to activated microglia and the presence of ERV-derived proteins in aggregate-like structures. This study demonstrates that brain development is a critical period for the silencing of ERVs and provides causal in vivo evidence demonstrating that transcriptional activation of ERV in neurons results in an inflammatory response.

Transposable Elements: A Common Feature of Neurodevelopmental and Neurodegenerative Disorders.

The etiology of most neurological disorders is poorly understood and current treatments are largely ineffective. New ideas and concepts are therefore vitally important for future research in this area. This review explores the concept that dysregulation of transposable elements (TEs) contributes to the appearance and pathology of neurodevelopmental and neurodegenerative disorders. Despite TEs making up at least half of the human genome, they are vastly understudied in relation to brain disorders. However, recent advances in sequencing technologies and gene editing approaches are now starting to unravel the pathological role of TEs. Aberrant activation of TEs has been found in many neurological disorders; the resulting pathogenic effects, which include alterations of gene expression, neuroinflammation, and direct neurotoxicity, are starting to be resolved. An increased understanding of the relationship between TEs and pathological processes in the brain improves the potential for novel diagnostics and interventions for brain disorders.

Organisational models of health services for children and adolescents in out-of-home care: Health technology assessment.

AIM: Decades of research confirm that children and adolescents in out-of-home care (foster family, residential care) have much greater health care needs than their peers. A systematic literature review was conducted to evaluate organisational health care models for this vulnerable group. METHODS: A systematic literature search was undertaken of the following databases: Academic Search Elite, CENTRAL, Cochrane Database of Systematic Reviews, Cinahl, DARE, ERIC, HTA, PsycInfo, Psychology and Behavioural Sciences Collection, PubMed, SocIndex. Randomised and non-randomised controlled trials were to be included. Two pairs of reviewers independently assessed abstracts of the identified published papers. Abstracts meeting the inclusion criteria were ordered in full text. Each article was reviewed independently, by pairs of reviewers. A joint assessment was made based on the inclusion criteria and relevance. Cases of disagreement were resolved by consensus discussion. RESULTS: No study with low or medium risk of bias was identified. CONCLUSION: In the absence of studies of acceptable quality, it is not possible to assess the impact of organisational models intended to ensure adequate health and dental care for children and adolescents in out-of-home care. Therefore, well-designed follow-up studies should be conducted following the implementation of such models.

Cost-effectiveness of a high-intensity versus a low-intensity smoking cessation intervention in a dental setting: long-term follow-up.

OBJECTIVES: The aim of this study was to conduct a cost-effectiveness analysis (CEA) of a high-intensity and a low-intensity smoking cessation treatment programme (HIT and LIT) using long-term follow-up effectiveness data and to validate the cost-effectiveness results based on short-term follow-up. DESIGN AND OUTCOME MEASURES: Intervention effectiveness was estimated in a randomised controlled trial as numbers of abstinent participants after 1 and 5-8 years of follow-up. The economic evaluation was performed from a societal perspective using a Markov model by estimating future disease-related costs (in Euro (€) 2018) and health effects (in quality-adjusted life-years (QALYs)). Programmes were explicitly compared in an incremental analysis, and the results were presented as an incremental cost-effectiveness ratio. SETTING: The study was conducted in dental clinics in Sweden. PARTICIPANTS: 294 smokers aged 19-71 years were included in the study. INTERVENTIONS: Behaviour therapy, coaching and pharmacological advice (HIT) was compared with one counselling session introducing a conventional self-help programme (LIT). RESULTS: The more costly HIT led to higher number of 6-month continuous abstinent participants after 1 year and higher number of sustained abstinent participants after 5-8 years, which translates into larger societal costs avoided and health gains than LIT. The incremental cost/QALY of HIT compared with LIT amounted to €918 and €3786 using short-term and long-term effectiveness, respectively, which is considered very cost-effective in Sweden. CONCLUSION: CEA favours the more costly HIT if decision makers are willing to spend at least €4000/QALY for tobacco cessation treatment.

The centrosome protein AKNA regulates neurogenesis via microtubule organization.

The expansion of brain size is accompanied by a relative enlargement of the subventricular zone during development. Epithelial-like neural stem cells divide in the ventricular zone at the ventricles of the embryonic brain, self-renew and generate basal progenitors1 that delaminate and settle in the subventricular zone in enlarged brain regions2. The length of time that cells stay in the subventricular zone is essential for controlling further amplification and fate determination. Here we show that the interphase centrosome protein AKNA has a key role in this process. AKNA localizes at the subdistal appendages of the mother centriole in specific subtypes of neural stem cells, and in almost all basal progenitors. This protein is necessary and sufficient to organize centrosomal microtubules, and promote their nucleation and growth. These features of AKNA are important for mediating the delamination process in the formation of the subventricular zone. Moreover, AKNA regulates the exit from the subventricular zone, which reveals the pivotal role of centrosomal microtubule organization in enabling cells to both enter and remain in the subventricular zone. The epithelial-to-mesenchymal transition is also regulated by AKNA in other epithelial cells, demonstrating its general importance for the control of cell delamination.

Economic evaluation of a brief counselling for smoking cessation in dentistry: a case study comparing two health economic models.

OBJECTIVES: This study aimed to compare the cost-effectiveness estimates of a brief counselling of smoking cessation in dentistry by using two different health economic models. DESIGN AND OUTCOME MEASURES: Intervention effectiveness was estimated in a cluster randomised controlled trial. The number of quitters was estimated based on 7-day abstinence and on smoking reduction at follow-up. Health economic evaluation was performed using two models: (1) a population-based model employing potential impact fractions and (2) a Markov model estimating the cost-effectiveness of the intervention for the actual participants. The evaluation was performed from healthcare and societal perspectives, and health gains were expressed in quality-adjusted life-years (QALYs). SETTING: Dental clinics in Sweden. PARTICIPANTS: 205 Swedish smokers aged 20-75 years. INTERVENTIONS: A brief, structured behavioural intervention was compared with 'usual care'. RESULTS: The cost per quitter was US$552 in the intervention and US$522 in the 'usual care' condition. The net saving estimated with the population-based model was US$17.3 million for intervention and US$49.9 million for 'usual care', with health gains of 1428 QALYs and 2369 QALYs, respectively, for the whole Swedish population during 10 years. The intervention was thus dominated by 'usual care'. The reverse was true when using the Markov model, showing net societal savings of US$71 000 for the intervention and US$57000 for 'usual care', with gains of 5.42 QALYs and 4.74 QALYs, respectively, for lifelong quitters. CONCLUSION: The comparison of intervention and 'usual care' derived from small-scale studies may be highly sensitive to the choice of the model used to calculate cost-effectiveness. TRIAL REGISTRATION: The cluster randomised trial is registered in the ISRCTN register of controlled trials with identification number ISRCTN50627997.

Economic and social impact of diabetes mellitus in a low-income country: A case-control study in Sudan.

BACKGROUND: Diabetes mellitus accounts for 11% of total health expenditure worldwide, and most people with diabetes live in low- and middle-income countries. The present study examined the economic and social effects attributed to diabetes in Sudan by calculating out-of-pocket medical expenses and the health and social effects of the disease for people with diabetes (n = 375) and their families compared with a non-diabetic control group (n = 375), matched for age, sex, and residence area. METHODS: Data were obtained in 2013 in four states within the Sudan, via structured interviews, using instruments from the International Diabetes Federation. Descriptive statistics were used to analyze differences between case and control participants. RESULTS: The median total annual medical expenditure was fourfold higher for people with than without diabetes (US$579 vs US$148, respectively). Annual mean expenditure was 85% higher for those with diabetes (US$1004 vs US$544). People with diabetes were also significantly more likely to suffer from serious comorbidities, such as cardiovascular disorders and foot ulcers, compared with control participants. Moreover, those with diabetes reported a higher proportion of personal adverse social effects, such as being prevented from doing paid work or participating in education, both for themselves and their families. CONCLUSIONS: The high economic burden and adverse social effects on people with diabetes and their families in Sudan call for the development of evidence-based policy and program strategies for the prevention and management of diabetes, with an emphasis on low-resource communities.

Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability.

We report that astrocytic insulin signaling co-regulates hypothalamic glucose sensing and systemic glucose metabolism. Postnatal ablation of insulin receptors (IRs) in glial fibrillary acidic protein (GFAP)-expressing cells affects hypothalamic astrocyte morphology, mitochondrial function, and circuit connectivity. Accordingly, astrocytic IR ablation reduces glucose-induced activation of hypothalamic pro-opio-melanocortin (POMC) neurons and impairs physiological responses to changes in glucose availability. Hypothalamus-specific knockout of astrocytic IRs, as well as postnatal ablation by targeting glutamate aspartate transporter (GLAST)-expressing cells, replicates such alterations. A normal response to altering directly CNS glucose levels in mice lacking astrocytic IRs indicates a role in glucose transport across the blood-brain barrier (BBB). This was confirmed in vivo in GFAP-IR KO mice by using positron emission tomography and glucose monitoring in cerebral spinal fluid. We conclude that insulin signaling in hypothalamic astrocytes co-controls CNS glucose sensing and systemic glucose metabolism via regulation of glucose uptake across the BBB.

The choroid plexuses and their impact on developmental neurogenesis.

During brain development the neural stem cells are regulated by both intrinsic and extrinsic sources. One site of origin of extrinsic regulation is the developing choroid plexuses, primely situated inside the cerebral ventricles. The choroid plexuses are very active in terms of both secretion and barrier function as soon as they appear during development and control the production and contents of cerebrospinal fluid (CSF). This suggests that regulated secretion of signaling molecules from the choroid plexuses into CSF can regulate neural stem cell behavior (as they are in direct contact with CSF) and thereby neurogenesis and brain development. Here, choroid plexus development, particularly with regards to molecular regulation and specification, is reviewed. This is followed by a review and discussion of the role of the developing choroid plexuses in brain development. In particular, recent evidence suggests a region-specific reciprocal regulation between choroid plexuses and the neural stem cells. This is accomplished by site-specific secretion of signaling molecules from the different choroid plexuses into CSF, as well as brain region specific competence of the neural stem cells to respond to the signaling molecules present in CSF. In conclusion, although in its infancy, the field of choroid plexus regulation of neurogenesis has already and will likely continue to shed new light on our understanding of the control and fine-tuning of overall brain development.