The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, oncological, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. The findings of the Rotterdam Study have been presented in over a 1,000 research articles and reports (see www.erasmus-epidemiology.nl/rotterdamstudy). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods.

/pdf/the-rotterdam-study-objectives-and-design-update-2n3pqovgsq.pdf

The Rotterdam Study: Objectives and design update

The Generation R Study is a population-based prospective cohort study from fetal life until young adulthood. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health during fetal life, childhood and adulthood. The study focuses on four primary areas of research: (1) growth and physical development; (2) behavioural and cognitive development; (3) diseases in childhood; and (4) health and healthcare for pregnant women and children. In total, 9,778 mothers with a delivery date from April 2002 until January 2006 were enrolled in the study. General follow-up rates until the age of 4 years exceed 75%. Data collection in mothers, fathers and preschool children included questionnaires, detailed physical and ultrasound examinations, behavioural observations, and biological samples. A genome wide association screen is available in the participating children. Regular detailed hands on assessment are performed from the age of 5 years onwards. Eventually, results forthcoming from the Generation R Study have to contribute to the development of strategies for optimizing health and healthcare for pregnant women and children.

/pdf/the-generation-r-study-design-and-cohort-update-2010-4gpvb9canr.pdf

The Generation R Study: design and cohort update 2010

Compromised function of regulatory T cells in rheumatoid arthritis: Reversal by anti-TNF alpha therapy

Cerebrospinal fluid (CSF) is a vital liquid, providing nutrients and signaling molecules and clearing out toxic by-products from the brain. The CSF is produced by the choroid plexus (ChP), a protective epithelial barrier that also prevents free entry of toxic molecules or drugs from the blood. Here, we establish human ChP organoids with a selective barrier and CSF-like fluid secretion in self-contained compartments. We show that this in vitro barrier exhibits the same selectivity to small molecules as the ChP in vivo and that ChP-CSF organoids can predict central nervous system (CNS) permeability of new compounds. The transcriptomic and proteomic signatures of ChP-CSF organoids reveal a high degree of similarity to the ChP in vivo. Finally, the intersection of single-cell transcriptomics and proteomic analysis uncovers key human CSF components produced by previously unidentified specialized epithelial subtypes.

https://science.sciencemag.org/content/sci/early/2020/06/10/science.aaz5626.full.pdf

Human CNS barrier-forming organoids with cerebrospinal fluid production

Hemorrhagic transformation (HT) is a frequent complication of acute ischemic stroke that is especially common after thrombolytic therapy. The risk of HT limits the applicability of tissue plasminogen activator (tPA). Here, we sought to review the rate, classification, predictors, possible mechanism, and clinical outcomes of HT, as well as existing therapeutic approaches, in order to call attention to the current challenges in the treatment of this complication.

https://atm.amegroups.com/article/download/4335/5191

Hemorrhagic transformation after cerebral infarction: current concepts and challenges.

Objective Cerebral autoregulation (CA) is the mechanism by which constant cerebral blood flow is maintained despite changes in cerebral perfusion pressure. CA can be evaluated by dynamic monitoring of cerebral blood flow velocity (CBFV) with transcranial Doppler sonography (TCD). The present study aimed to explore CA in chronic anxiety. Methods Subjects with Hamilton anxiety scale scores ≥14 were enrolled and the dynamic changes of CBFV in response to an orthostatic challenge were investigated using TCD. Results In both the anxious and the healthy subjects, the mean CBFV was significantly lower in the upright position than when supine. However, the CBFV changes from supine to upright differed between the anxious and the healthy groups. Anxious subjects showed more pronounced decreases in CBFV with abrupt standing. Conclusion Our results indicate that cerebrovascular modulation is compromised in chronic anxiety; anxious subjects have some insufficiency in maintaining cerebral perfusion after pos- tural change. Given the fact that anxiety and impaired CA are associated with cardiovascular disease, early ascertainment of compromised cerebrovascular modulation using TCD might suggest interventional therapies in the anxious population, and improve the primary prevention of cardiovascular disease.

/pdf/compromised-cerebrovascular-modulation-in-chronic-anxiety-3qd1r6cwi6.pdf

Compromised cerebrovascular modulation in chronic anxiety: evidence from cerebral blood flow velocity measured by transcranial Doppler sonography

In the article by Prakash et al. [1], a relation between prevalence of headache and the latitude was reviewed. Although the profile of headache matches with seasonal variations and geographical distribution of serum vitamin D levels, we believe that it is currently far-fetched to correlate headache with vitamin D insufficiency. Several lines of epidemiological and experimental evidence have been proposed to support links of vitamin D with various conditions or diseases beyond bone health, including muscle function, autoimmune diseases, cancer, cardiovascular diseases (CVD), hypertension, diabetes, inflammatory diseases, all-cause mortality, etc. [2]. The relations between vitamin D insufficiency and human diseases, especially multiple sclerosis has been partly explained by the seasonal and geographical variations of serum vitamin D, which has further been confirmed by decreased incidence and severity of multiple sclerosis by vitamin D supplementation [3]. In this regard, either observational studies to find decreased levels of serum vitamin D in patients with headache or placebo-controlled studies to observe the therapeutic effects of vitamin D in headache are still lacking. The geographical features of apolipoprotein E(apoE) allele [4] and serum vitamin D concentrations [5], both of which are associated with autoimmune diseases such as multiple sclerosis, also lead us to assume that there might be some correlations between apoE epsilon 4 allele and vitamin D. However, since robust evidence is lacking, from the current knowledge, we can only ascribe this to coincidence, unless new evidence can be found in future studies. Otherwise wearing more clothes may also be linked to the higher incidence of stoke in cold areas. In summary, it is promising to confirm a positive correlation between headache and vitamin D insufficiency in that it may provide new therapeutic strategies for migraine as well as other types of headaches. However, further investigations are still needed to find out such a relation between headache and vitamin D.

/pdf/is-headache-related-with-vitamin-d-insufficiency-7vusitelks.pdf

Is headache related with vitamin D insufficiency

We read with interest Ruth Williams’ report on the use of telemedicine and information technologies in neurology. We provide present and future thoughts and concerns about this new technology that might help underserved areas with no neurologists. First, we believe that in the immediate future, telemedicine has great potential to electronically bridge the gap between underserved areas and centres that have specialty neurologists, without having to increase the overall supply of neurologists. Teleneurology can provide instant neurologist input via secure internet-based video interaction, without specialists or patients having to travel long distances. Furthermore, the supply of neurologists is not expected to substantially increase to match the expected rise in age-related neurological disease in the ageing population. The eff ect of teleneurology might be greatest in acute stroke—a medical emergency—especially in view of the cost-eff ectiveness of thrombolytic therapy, which can now be given up to 4·5 h after onset of stroke. However, what happens when the telemedicine operator does not possess the requisite clinical skills in neurology to diagnose and manage the patient, or when the virtual consultative modality does not result in an adequately reliable and valid examination? In the USA, there are now commercial robots with specialised arms that not only function as electronic stethoscopes and otoscopes, but that can also focus on various parts of the neurological examination—eg, extraocular muscle movements. Even though a patient can be examined remotely by a robot, it is the knowledge, experience, and judgment of the interpreting physician that results in accurate diagnoses, appropriate clinical management, and reasonable predictions of prognosis. Although the technological advances are fascinating, the most crucial element of any telemedicine interaction is still the human connection between a patient who needs help and a physician who cares. An unskilled telemedicine operator is no more capable of properly treating the patient from a distance than is a similarly untrained live physician on-site. This concept is especially important in neurology—a specialty in which raw clinical data and fi ndings are generally not equivalent to diagnoses. There is a growing number of anecdotal reports in the USA about the use of commercially available robots with remote, non-neurologist operators in place of neurologists for both acute and non-acute diagnosis and management. Similarly, the audio–video telemedicine consultative modality, which has been well studied in acute stroke, is being broadly extended into many other neurological subspecialty arenas without suffi ciently supportive evidence. The resulting diagnoses have not always been correct, and the treatments not always appropriate. In some cases, existing contracts between a hospital and a robot service have superseded the use of an on-site consulting neurologist, even when one was readily available. Teleneurology can successfully be an adjunct to, an extension of, or even a replacement for, on-site clinical neurology, but only when directed by qualifi ed neurologists. Unfortunately, commercial incentives could potentially override and interfere with the professional obligations to the patient.

Diagnosis of posterior reversible encephalopathy syndrome: does DWI help?

Role of T Regulatory Cells in the Pathogenesis of Asthma

Dear Editors,Tian and colleagues summarized the role of Th22 cells and IL-22 in inflammatory and autoimmune diseases [1]. Their review was well written, whereas it might be strengthened by suppleme...

Comment and reply on:Emerging role of Th22 and IL-22 in multiple sclerosis, an autoimmune disease in the central nervous system

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