Molecular biology of the blood-brain and the blood-cerebrospinal fluid barriers: similarities and differences

Efficient processing of information by the central nervous system (CNS) represents an important evolutionary advantage. Thus, homeostatic mechanisms have developed that provide appropriate circumstances for neuronal signaling, including a highly controlled and stable microenvironment. To provide such a milieu for neurons, extracellular fluids of the CNS are separated from the changeable environment of blood at three major interfaces: at the brain capillaries by the blood-brain barrier (BBB), which is localized at the level of the endothelial cells and separates brain interstitial fluid (ISF) from blood; at the epithelial layer of four choroid plexuses, the blood-cerebrospinal fluid (CSF) barrier (BCSFB), which separates CSF from the CP ISF, and at the arachnoid barrier. The two barriers that represent the largest interface between blood and brain extracellular fluids, the BBB and the BCSFB, prevent the free paracellular diffusion of polar molecules by complex morphological features, including tight junctions (TJs) that interconnect the endothelial and epithelial cells, respectively. The first part of this review focuses on the molecular biology of TJs and adherens junctions in the brain capillary endothelial cells and in the CP epithelial cells. However, normal function of the CNS depends on a constant supply of essential molecules, like glucose and amino acids from the blood, exchange of electrolytes between brain extracellular fluids and blood, as well as on efficient removal of metabolic waste products and excess neurotransmitters from the brain ISF. Therefore, a number of specific transport proteins are expressed in brain capillary endothelial cells and CP epithelial cells that provide transport of nutrients and ions into the CNS and removal of waste products and ions from the CSF. The second part of this review concentrates on the molecular biology of various solute carrier (SLC) transport proteins at those two barriers and underlines differences in their expression between the two barriers. Also, many blood-borne molecules and xenobiotics can diffuse into brain ISF and then into neuronal membranes due to their physicochemical properties. Entry of these compounds could be detrimental for neural transmission and signalling. Thus, BBB and BCSFB express transport proteins that actively restrict entry of lipophilic and amphipathic substances from blood and/or remove those molecules from the brain extracellular fluids. The third part of this review concentrates on the molecular biology of ATP-binding cassette (ABC)-transporters and those SLC transporters that are involved in efflux transport of xenobiotics, their expression at the BBB and BCSFB and differences in expression in the two major blood-brain interfaces. In addition, transport and diffusion of ions by the BBB and CP epithelium are involved in the formation of fluid, the ISF and CSF, respectively, so the last part of this review discusses molecular biology of ion transporters/exchangers and ion channels in the brain endothelial and CP epithelial cells

Temporal Trend and Spatial Distribution of Drug Poisoning in Semnan Province: A Retrospective Longitudinal Study

Background: Substance abuse and the risks of its consequences are the major public health problems in the world and Iran. Objectives: The objective of the present study is determination the epidemiological status and spatial distribution of high-risk and low-risk clusters along with estimating the relative risk of drug poisoning in Semnan in 8 years. Methods: A descriptive-analytical and retrospective longitudinal study was conducted that examined all 3360 poisoned patients who referred to the hospitals of Semnan province from 2011-2018. The total number of visits was received and analyzed by year with the relevant diagnostic code in ICD-10 from hospitals of the province, and data were analyzed using Joinpoint regression analysis, global Moran’s index and Kuldorff’s spatial statistic scan at a significant level of 0.05. Results: The number of clients varied from 219 in 2011 to 570 in 2015. The patients’ mean age was 26.7 years. The average annual number of cases per one hundred thousand individuals (annual cases/100000) was 598.4. The AAPC of the incidence of drug poisoning was 9.8 and significant in the whole province, demonstrating that the incidence of poisoning increased by an average of 9.8 per year in the whole province from 2011 to 2018. Semnan County with LLR = 533.07 was the most likely low-risk cluster, and Shahroud County was the most likely high-risk cluster with LLR = 219.94. Conclusions: Drug policies need to be adapted to the geographical differences in the place death. After clustering regions in poisoning incidents, the necessary interventions can be concentrated for these specific geographical locations. © 2022, Author(s)

Psychometric Characteristics of Childbearing Motivation Questionnaire: A Review

Background: Considering the important role of understanding the childbearing motivations in counseling services about childbearing behavior, and need for applying a valid and reliable instrument to assess it in Iranian society, this study was conducted to determine Childbearing motivation. Questionnaire was validated in two versions including Persian and English. The review aimed to comprehensively review the validity and reliability of Childbearing Motivation Questionnaire to provide comprehensive information to health providers. Materials and Methods: We conducted an extensive search on online databases (Medline, EMBASE. Web of Science, Scopus, Cochrane Library, and CINAHL) from inception until September 2019. The following keywords were used: ("Childbearing Questionnaire" OR "CBQ") AND ("Factor Analysis" OR "Exploratory Factor Analysis" OR "Confirmatory Factor Analysis" OR "Reliability" OR "Psychometric" OR "Cronbach's alpha" OR "Test-retest Reliability" OR "Intra-class Correlation Coefficient" OR "ICC"). COSMIN checklist was used to assess the methodological quality of studies. Results: Three studies were included in review. Intra-class correlation coefficient (ICC), Cronbach's alpha coefficient and the test-retest reliability indicated satisfactory reliability of the CBQ. Original version of Childbearing Motivation Questionnaire was developed by Miller (1995). In Persian version, original model did not show the 'acceptable' fit. After removing eight factors with low loading and two correlated error terms, modified model was found to have "adequate" fitness (Comparative Fit Index (CFI=.91), Tucker-Lewis Index (TLI=.90), Root Mean Square Error of Approximation (RMSEA=.04), and Chi-square to degree of freedom x2/df=1.92). Conclusion: The Persian and English version of childbearing motivation has good construct validity and reliability. Future research needs to test six-factor model with 49 total items and modified model with 43 items in various populations

Social Work and Non-Pharmacological Treatment on Iranian Children with Hemophilia: A Systematic Review

Background: With the establishment of new technologies in the search for a cure for hemophilia, non-pharmacological treatments have had a more important role in increasing life expectancy, quality of life of children suffering from hemophilia disorders. The aim of the systematic review was a comprehensive understanding of Non-pharmacological treatment on Iranian children with hemophilia. Materials and Methods: In this systematic review, articles published in national (Irandoc, Magiran, Medlib, and SID), and international databases (Medline via PubMed, EMBASE, Web of Science, Scopus and Cochran Central Register of Controlled Trials) were searched without any time limitation till to June, 2019. The keywords of the search include (Child OR Children) AND (Hemophilia OR Hemophiliac) AND (Iranian or Iranian). To assess the quality of the articles intered into the search, we utilized the 5-item Jadad scale. Results: Six studies were included in the systematic review. The achieved results suggested psychological training can alleviate the test anxiety, life expectancy. Yoga has a significant role in lessening the rate of bleedings, referrals to the haemophilia clinic, and the school non-attendance. Body vibration training has some benefits such as quadriceps strength, bone mineral density, and the functional capacity. Program management by nurse or own children have significant improvement on quality of life of children suffering from hemophilia disorders. Conclusion: The achieved results suggested policymakers take heed of this novel treatment and non-pharmacological approaches such as psychological training, yoga, body vibration training and its effects on alleviating non-pharmacological treatment on children with hemophilia

Advantages and Disadvantages of Methadone among Children and Adults: A Systematic Review and Meta-Analysis

Background: Today, an increasing trend to methadone as an alternative maintenance treatment for opiate dependence in adults is observed; children for both intentional and accidental reasons are exposed to serious and fetal effects of methadone. We aimed to investigate effects of methadone on children and sexual functioning among adults in Iranian population. Materials and Methods: An extensive search was done in databases of Medline, EMBASE, Scopus, Cochrane, and Web of Science until August 2018. Two independent researchers screened articles, and categorized them based on the evaluated outcomes and overall effect size was presented. After excluding the duplicated, irrelevant and low-quality articles, eligible ones were enrolled in the meta-analysis. Finally, pooled effect size was presented as standardized mean difference (SMD) or pooled prevalence with 95 confidence interval (95 CI). Results: Methadone was found to be more effective than morphine on neonatal abstinence syndrome. The first four most common symptoms of methadone poisoning were loss of consciousness (81), sleepiness (72), meiotic pupils (76), vomiting (56), and Apnea (48). The overall prevalence rate of sexual disorders and erectile dysfunction was 66.3 and 77.5, respectively. The subjects in methadone group were over 2.5-fold more likely to use condom during intercourse (p<0.001). The methadone therapy could lead to a significant reduction in orgasm functioning (p<0.001), and a significant improvement in libido (p=0.001). The methadone maintenance treatment (MMT) significantly resulted in decreased orgasm function and improved libido in males. Conclusion: Evidence suggests a positive impact of methadone maintenance treatment on risky sexual behaviors. Regarding the methadone poisoning effect on children, people should be informed by health care providers about serious and fetal effects on children

Text message alerts to emergency physicians identifying potential study candidates increase clinical trial enrollment.

Prospective enrollment of research subjects in the fast-paced emergency department (ED) is challenging. We sought to develop a software application to increase real-time clinical trial enrollment during an ED visit. The Prospective Intelligence System for Clinical Emergency Services (PISCES) scans the electronic health record during ED encounters for preselected clinical characteristics of potentially eligible study participants and notifies the treating physician via mobile phone text alerts. PISCES alerts began 3 months into a cluster randomized trial of an electronic health record-based risk stratification tool for pediatric abdominal pain in 11 Northern California EDs. We compared aggregate enrollment before (2577 eligible patients, October 2016 to December 2016) and after (12 049 eligible patients, January 2017 to January 2018) PISCES implementation. Enrollment increased from 10.8% to 21.1% following PISCES implementations (P &lt; .001). PISCES significantly increased study enrollment and can serve as a valuable tool to assist prospective research enrollment in the ED