Ascorbic acid and its transporter SVCT2, affect radial glia cells differentiation in postnatal stages.

Radial glia (RG) cells generate neurons and glial cells that make up the cerebral cortex. Both in rodents and humans, these stem cells remain for a specific time after birth, named late radial glia (lRG). The knowledge of lRG and molecules that may be involved in their differentiation is based on very limited data. We analyzed whether ascorbic acid (AA) and its transporter SVCT2, are involved in lRG cells differentiation. We demonstrated that lRG cells are highly present between the first and fourth postnatal days. Anatomical characterization of lRG cells, revealed that lRG cells maintained their bipolar morphology and stem-like character. When lRG cells were labeled with adenovirus-eGFP at 1 postnatal day, we detected that some cells display an obvious migratory neuronal phenotype, suggesting that lRG cells continue generating neurons postnatally. Moreover, we demonstrated that SVCT2 was apically polarized in lRG cells. In vitro studies using the transgenic mice SVCT2+/- and SVCT2tg (SVCT2-overexpressing mouse), showed that decreased SVCT2 levels led to accelerated differentiation into astrocytes, whereas both AA treatment and elevated SVCT2 expression maintain the lRG cells in an undifferentiated state. In vivo overexpression of SVCT2 in lRG cells generated cells with a rounded morphology that were migratory and positive for proliferation and neuronal markers. We also examined mediators that can be involved in AA/SVCT2-modulated signaling pathways, determining that GSK3-ß through AKT, mTORC2, and PDK1 is active in brains with high levels of SVCT2/AA. Our data provide new insights into the role of AA and SVCT2 in late RG cells.

Corrigendum: New insights into hypothalamic neurogenesis disruption after acute and intense stress: implications for microglia and inflammation.

[This corrects the article DOI: 10.3389/fnins.2023.1190418.].

Hyperglycemia increases SCO-spondin and Wnt5a secretion into the cerebrospinal fluid to regulate ependymal cell beating and glucose sensing.

Hyperglycemia increases glucose concentrations in the cerebrospinal fluid (CSF), activating glucose-sensing mechanisms and feeding behavior in the hypothalamus. Here, we discuss how hyperglycemia temporarily modifies ependymal cell ciliary beating to increase hypothalamic glucose sensing. A high level of glucose in the rat CSF stimulates glucose transporter 2 (GLUT2)-positive subcommissural organ (SCO) cells to release SCO-spondin into the dorsal third ventricle. Genetic inactivation of mice GLUT2 decreases hyperglycemia-induced SCO-spondin secretion. In addition, SCO cells secrete Wnt5a-positive vesicles; thus, Wnt5a and SCO-spondin are found at the apex of dorsal ependymal cilia to regulate ciliary beating. Frizzled-2 and ROR2 receptors, as well as specific proteoglycans, such as glypican/testican (essential for the interaction of Wnt5a with its receptors) and Cx43 coupling, were also analyzed in ependymal cells. Finally, we propose that the SCO-spondin/Wnt5a/Frizzled-2/Cx43 axis in ependymal cells regulates ciliary beating, a cyclic and adaptive signaling mechanism to control glucose sensing.

New insights into hypothalamic neurogenesis disruption after acute and intense stress: implications for microglia and inflammation.

In recent years, the hypothalamus has emerged as a new neurogenic area, capable of generating new neurons after development. Neurogenesis-dependent neuroplasticity seems to be critical to continuously adapt to internal and environmental changes. Stress is a potent environmental factor that can produce potent and enduring effects on brain structure and function. Acute and chronic stress is known to cause alterations in neurogenesis and microglia in classical adult neurogenic regions such as the hippocampus. The hypothalamus is one of the major brain regions implicated in homeostatic stress and emotional stress systems, but little is known about the effect of stress on the hypothalamus. Here, we studied the impact of acute and intense stress (water immersion and restrain stress, WIRS), which may be considered as an inducer of an animal model of posttraumatic stress disorder, on neurogenesis and neuroinflammation in the hypothalamus of adult male mice, focusing on three nuclei: PVN, VMN and ARC, and also in the periventricular area. Our data revealed that a unique stressor was sufficient to provoke a significant impact on hypothalamic neurogenesis by inducing a reduction in the proliferation and number of immature neurons identified as DCX+ cells. These differences were accompanied by marked microglial activation in the VMN and ARC, together with a concomitant increase in IL-6 levels, indicating that WIRS induced an inflammatory response. To investigate the possible molecular mechanisms responsible for neuroplastic and inflammatory changes, we tried to identify proteomic changes. The data revealed that WIRS induced changes in the hypothalamic proteome, modifying the abundance of three and four proteins after 1 h or 24 h of stress application, respectively. These changes were also accompanied by slight changes in the weight and food intake of the animals. These results are the first to show that even a short-term environmental stimulus such as acute and intense stress can have neuroplastic, inflammatory, functional and metabolic consequences on the adult hypothalamus.

Tear gas exposure and its association with respiratory emergencies in infants and older adults during the social uprising of 2019 in Chile: an observational, longitudinal, repeated measures study.

OBJECTIVE: To evaluate if extensive use of tear gas during the Chilean social uprising of 2019 was associated with a higher frequency of respiratory emergencies and bronchial diseases in a residential vulnerable population. DESIGN: Observational, longitudinal, repeated measures study. SETTINGS: Six healthcare centres (one emergency department and five urgent care centres) in the city of Concepción, Chile during 2018 and 2019. PARTICIPANTS: This study was conducted on daily respiratory emergencies and diagnosis. Daily frequency of urgency and emergency visits are administrative data, publicly available and previously de-identified. PRIMARY AND SECONDARY OUTCOME MEASURES: Absolute and relative frequency of daily respiratory emergencies in infants and older adults. A secondary outcome was the relative frequency of bronchial diseases (International Classification of Diseases 10th Revision, ICD-10: J20-J21; J40-J46) in both age groups. We finally measured the rate ratio (RR) of bronchial diseases above the daily grand mean, since the number of visits with these diagnoses in several days was zero. Tear gas exposure was assessed as the uprising period. Models were adjusted by weather and air pollution information. RESULTS: Percentage of respiratory emergencies during the uprising rose by 1.34 percentage points (95% CI 1.26 to 1.43) in infants and 1.44 percentage points (95% CI 1.34 to 1.55) in older adults. In infants, the emergency department experienced a larger increment in respiratory emergencies (6.89 percentage points; 95% CI 1.58 to 2.28) than the urgent care centres (1.67 percentage points; 95% CI 1.46 to 1.90). The RR of bronchial diseases above the daily grand mean during the uprising period was 1.34 in infants (95% CI 1.15 to 1.56) and 1.50 in older adults (95% CI 1.28 to 1.75). CONCLUSIONS: The massive use of tear gas increases the frequency and probability of respiratory emergencies and particularly bronchial diseases in the vulnerable population; we recommend revising public policy to restrict its use.

Vitamin C Deficiency Reduces Neurogenesis and Proliferation in the SVZ and Lateral Ventricle Extensions of the Young Guinea Pig Brain.

Although scurvy, the severe form of vitamin C deficiency, has been almost eradicated, the prevalence of subclinical vitamin C deficiency is much higher than previously estimated and its impact on human health might not be fully understood. Vitamin C is an essential molecule, especially in the central nervous system where it performs numerous, varied and critical functions, including modulation of neurogenesis and neuronal differentiation. Although it was originally considered to occur only in the embryonic brain, it is now widely accepted that neurogenesis also takes place in the adult brain. The subventricular zone (SVZ) is the neurogenic niche where the largest number of new neurons are born; however, the effect of vitamin C deficiency on neurogenesis in this key region of the adult brain is unknown. Therefore, through BrdU labeling, immunohistochemistry, confocal microscopy and transmission electron microscopy, we analyzed the proliferation and cellular composition of the SVZ and the lateral ventricle (LVE) of adult guinea pigs exposed to a vitamin-C-deficient diet for 14 and 21 days. We found that neuroblasts in the SVZ and LVE were progressively and significantly decreased as the days under vitamin C deficiency elapsed. The neuroblasts in the SVZ and LVE decreased by about 50% in animals with 21 days of deficiency; this was correlated with a reduction in BrdU positive cells in the SVZ and LVE. In addition, the reduction in neuroblasts was not restricted to a particular rostro-caudal area, but was observed throughout the LVE. We also found that vitamin C deficiency altered cellular morphology at the ultrastructural level, especially the cellular and nuclear morphology of ependymal cells of the LVE. Therefore, vitamin C is essential for the maintenance of the SVZ cell populations required for normal activity of the SVZ neurogenic niche in the adult guinea pig brain. Based on our results from the guinea pig brain, we postulate that vitamin C deficiency could also affect neurogenesis in the human brain.

Is IIIG9 a New Protein with Exclusive Ciliary Function? Analysis of Its Potential Role in Cancer and Other Pathologies.

The identification of new proteins that regulate the function of one of the main cellular phosphatases, protein phosphatase 1 (PP1), is essential to find possible pharmacological targets to alter phosphatase function in various cellular processes, including the initiation and development of multiple diseases. IIIG9 is a regulatory subunit of PP1 initially identified in highly polarized ciliated cells. In addition to its ciliary location in ependymal cells, we recently showed that IIIG9 has extraciliary functions that regulate the integrity of adherens junctions. In this review, we perform a detailed analysis of the expression, localization, and function of IIIG9 in adult and developing normal brains. In addition, we provide a 3D model of IIIG9 protein structure for the first time, verifying that the classic structural and conformational characteristics of the PP1 regulatory subunits are maintained. Our review is especially focused on finding evidence linking IIIG9 dysfunction with the course of some pathologies, such as ciliopathies, drug dependence, diseases based on neurological development, and the development of specific high-malignancy and -frequency brain tumors in the pediatric population. Finally, we propose that IIIG9 is a relevant regulator of PP1 function in physiological and pathological processes in the CNS.

In vivo subchronic effects of ciguatoxin-related compounds, reevaluation of their toxicity.

Ciguatoxins are marine compounds that share a ladder-shaped polyether structure produced by dinoflagellates of the genus Gambierdiscus and Fukuyoa, and include maitotoxins (MTX1 and MTX3), ciguatoxins (CTX3C) and analogues (gambierone), components of one of the most frequent human foodborne illness diseases known as ciguatera fish poisoning. This disease was previously found primarily in tropical and subtropical areas but nowadays, the dinoflagellates producers of ciguatoxins had spread to European coasts. One decade ago, the European Food Safety Authority has raised the need to complete the toxicological available data for the ciguatoxin group of compounds. Thus, in this work, the in vivo effects of ciguatoxin-related compounds have been investigated using internationally adopted guidelines for the testing of chemicals. Intraperitoneal acute toxicity was tested for maitotoxin 1 at doses between 200 and 3200 ng/kg and the acute oral toxicity of Pacific Ciguatoxin CTX3C at 330 and 1050 ng/kg and maitotoxin 1 at 800 ng/kg were also evaluated showing not effects on mice survival after a 96 h observation period. Therefore, for the following experiments the oral subchronic doses were between 172 and 1760 ng/kg for gambierone, 10 and 102 ng/kg for Pacific Ciguatoxin CTX3C, 550 and 1760 ng/kg for maitotoxin 3 and 800, 2560 and 5000 ng/kg for maitotoxin 1. The results presented here raise the need to reevaluate the in vivo activity of these agents. Although the intraperitoneal lethal dose of maitotoxin 1 is assumed to be 50 ng/kg, without chemical purity identifications and description of the bioassay procedures, in this work, an intraperitoneal lethal dose of 1107 ng/kg was obtained. Therefore, the data presented here highlight the need to use a common procedure and certified reference material to clearly establish the levels of these environmental contaminants in food.

Use of medical services in Chile: How sensitive are the results to different econometric models?

BACKGROUND: We compared different econometric specifications to model the use of medical services in Chile, focussing on visits to general practitioners and specialist physicians. METHODS: The evaluated models are the Poisson, Negative Binomial, Zero Inflated Poisson and Negative Binomial, two-step Hurdle model, sample-selection Poisson, and Latent Class model. These models were estimated using Chilean data for the years 2009 and 2015, separated by gender. RESULTS: Unlike previous literature that supported the use of the latent class model, our results show that the latent class model is not always the model with the best goodness of fit. Furthermore, the model with the best fit is not necessarily the model with the best predictive power. For instance, depending on the year and medical services, either the latent class model or the sample-selection Poisson model performs better than the other models. The results also show that the selection of the econometric model may have implications for the estimated influence that variables such as age, income, or affiliation to the public versus private sector have on the use of medical services. CONCLUSION: Using Chilean data, we have tested that the selection of an econometric method to model the use of medical services is not a problem with a unique answer. We recommend performing a sensitivity analysis of goodness of fit and predictive power between gender, healthcare services, or different years of datasets in future applications to be sure about the best model specification in each context.

IIIG9 inhibition in adult ependymal cells changes adherens junctions structure and induces cellular detachment.

Ependymal cells have multiple apical cilia that line the ventricular surfaces and the central canal of spinal cord. In cancer, the loss of ependymal cell polarity promotes the formation of different types of tumors, such as supratentorial anaplastic ependymomas, which are highly aggressive in children. IIIG9 (PPP1R32) is a protein restricted to adult ependymal cells located in cilia and in the apical cytoplasm and has unknown function. In this work, we studied the expression and localization of IIIG9 in the adherens junctions (cadherin/ß-catenin-positive junctions) of adult brain ependymal cells using confocal and transmission electron microscopy. Through in vivo loss-of-function studies, ependymal denudation (single-dose injection experiments of inhibitory adenovirus) was observed, inducing the formation of ependymal cells with a "balloon-like" morphology. These cells had reduced cadherin expression (and/or delocalization) and cleavage of the cell death marker caspase-3, with "cilia rigidity" morphology (probably vibrational beating activity) and ventriculomegaly occurring prior to these events. Finally, after performing continuous infusions of adenovirus for 14 days, we observed total cell denudation and reactive parenchymal astrogliosis. Our data confirmed that IIIG9 is essential for the maintenance of adherens junctions of polarized ependymal cells. Eventually, altered levels of this protein in ependymal cell differentiation may increase ventricular pathologies, such as hydrocephalus or neoplastic transformation.

Effects of precarious work on symptomatology of anxiety and depression in Chilean workers, a cross sectional study.

BACKGROUND: Precarious work is a broad definition for non-standard employment, often including unstable and insecure positions where workers permanently experience uncertainty; these types of jobs are growing steadily around the planet. Since the coup d'état in 1973, Chile has experienced a series of structural economic changes framed by neoliberal ideas cemented in the "Constitution of Pinochet." Precarious work in Chile is a direct consequence of these ideas. This multidimensional phenomenon has progressively been entering employment areas where it was not previously present. As a result, there has been a rise in work precarization and its full impact on health is not well known. The goal of this study was to estimate the association of work precariousness with mental health outcomes in Chilean workers. METHODS: Data were obtained from the Chilean Survey of Work and Health 2009-2010 (ENETS). Only valid records of salaried workers (excluding hourly-only or commission-only workers) in the private sector without missing values were included (n = 1900). After applying appropriate sampling weights, 1,461,727 workers were represented. Mental health was estimated as anxiety/depression levels using the 12-item General Health Questionnaire (GHQ-12). A multilevel multivariate generalized linear mixed model (GLMM) with negative binomial and log link distribution was used to study the association between precariousness and depression/anxiety. RESULTS: Looking at the overall precariousness scale (range from zero to four), we observed an increase of approximately 34% in the depression/anxiety score (scale range from 0 to 36) for every unit on the precarious work overall scale (Relative Risk = 1.34, 95% CI = 1.28, 1.42) controlling for age, sex, and occupational group. CONCLUSION: Precarious work was associated with anxiety and depression as measured with the 12-item General Health Questionnaire. Controlling for demographic variables changed neither the direction nor the magnitude of the association.

A Corporate Wellness Program and Nursing Home Employees' Health.

Background: Many employed Americans suffer from chronic conditions like obesity, diabetes, and cardiovascular diseases. Worksite wellness programs provide opportunities to introduce health promotion strategies. While there is evidence of the effectiveness of workplace health promotion, this is tempered by concern that benefits may be less available to low-wage workers with inflexible working conditions. Objective: The aim was to evaluate a workplace health promotion (WHP) in the long-term care sector (skilled nursing facilities). Methods: Nursing home employees from 18 facilities within a single company were surveyed by a standardized, self-administered questionnaire. A company-sponsored WHP program was offered to the facilities, which were free to take it up or not. We categorized the facilities by level of program adoption. Cross-sectional associations were estimated between program category and prevalence of individual-level worker health indicators, adjusting for center-level working conditions. Results: A total of 1,589 workers in 5 job categories completed the survey. Average levels of psychological demands and social support at work were relatively high. Supervisor support stood out as higher in centers with well-developed WHP programs, compared to centers with no programs. There were no differences among program levels for most health outcomes. Workers in centers with well-developed programs had slightly lower average body mass index and (unexpectedly) slightly lower prevalence of non-smoking and regular aerobic exercise. Conclusions: Only small health benefits were observed from well-developed programs and working conditions did not appear to confound the negative results. This low-intensity, low-resourced workplace health promotion program may have benefited a few individuals but seems to have had only modest influence on average levels of the measured health indicators. Many nursing home employees experience obstacles to health behaviors; approaches that provide more environmental and economic supports for healthy behaviors, such as Total Worker Health®, may yield larger health benefits.

Dehydroascorbic acid, the oxidized form of vitamin C, improves renal histology and function in old mice.

Oxidative stress and inflammation are crucial factors that increase with age. In the progression of multiple age-related diseases, antioxidants and bioactive compounds have been recognized as useful antiaging agents. Oxidized or reduced vitamin C exerts different actions on tissues and has different metabolism and uptake. In this study, we analyzed the antiaging effect of vitamin C, both oxidized and reduced forms, in renal aging using laser microdissection, quantitative reverse-transcription polymerase chain reaction, and immunohistochemical analyses. In the kidneys of old SAM mice (10 months of age), a model of accelerated senescence, vitamin C, especially in the oxidized form (dehydroascorbic acid [DHA]) improves renal histology and function. Serum creatinine levels and microalbuminuria also decrease after treatment with a decline in azotemia. In addition, sodium-vitamin C cotransporter isoform 1 levels, which were increased during aging, are normalized. In contrast, the pattern of glucose transporter 1 expression is not affected by aging or vitamin C treatment. We conclude that oxidized and reduced vitamin C are potent antiaging therapies and that DHA reverses the kidney damage observed in senescence-accelerated prone mouse 8 to a greater degree.

Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells.

BACKGROUND: In obstructive congenital hydrocephalus, cerebrospinal fluid accumulation is associated with high intracranial pressure and the presence of periventricular edema, ischemia/hypoxia, damage of the white matter, and glial reactions in the neocortex. The viability and short time effects of a therapy based on bone marrow-derived mesenchymal stem cells (BM-MSC) have been evaluated in such pathological conditions in the hyh mouse model. METHODS: BM-MSC obtained from mice expressing fluorescent mRFP1 protein were injected into the lateral ventricle of hydrocephalic hyh mice at the moment they present a very severe form of the disease. The effect of transplantation in the neocortex was compared with hydrocephalic hyh mice injected with the vehicle and non-hydrocephalic littermates. Neural cell populations and the possibility of transdifferentiation were analyzed. The possibility of a tissue recovering was investigated using 1H High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance (1H HR-MAS NMR) spectroscopy, thus allowing the detection of metabolites/osmolytes related with hydrocephalus severity and outcome in the neocortex. An in vitro assay to simulate the periventricular astrocyte reaction conditions was performed using BM-MSC under high TNFα level condition. The secretome in the culture medium was analyzed in this assay. RESULTS: Four days after transplantation, BM-MSC were found undifferentiated and scattered into the astrocyte reaction present in the damaged neocortex white matter. Tissue rejection to the integrated BM-MSC was not detected 4 days after transplantation. Hyh mice transplanted with BM-MSC showed a reduction in the apoptosis in the periventricular neocortex walls, suggesting a neuroprotector effect of the BM-MSC in these conditions. A decrease in the levels of metabolites/osmolytes in the neocortex, such as taurine and neuroexcytotoxic glutamate, also indicated a tissue recovering. Under high TNFα level condition in vitro, BM-MSC showed an upregulation of cytokine and protein secretion that may explain homing, immunomodulation, and vascular permeability, and therefore the tissue recovering. CONCLUSIONS: BM-MSC treatment in severe congenital hydrocephalus is viable and leads to the recovery of the severe neurodegenerative conditions in the neocortex. NMR spectroscopy allows to follow-up the effects of stem cell therapy in hydrocephalus.

Why does the adverse effect of inappropriate MRI for LBP vary by geographic location? An exploratory analysis.

BACKGROUND: Early magnetic resonance imaging (eMRI) for nonspecific low back pain (LBP) not adherent to clinical guidelines is linked with prolonged work disability. Although the prevalence of eMRI for occupational LBP varies substantially among states, it is unknown whether the risk of prolonged disability associated with eMRI varies according to individual and area-level characteristics. The aim was to explore whether the known risk of increased length of disability (LOD) associated with eMRI scanning not adherent to guidelines for occupational LBP varies according to patient and area-level characteristics, and the potential reasons for any observed variations. METHODS: A retrospective cohort of 59,360 LBP cases from 49 states, filed between 2002 and 2008, and examined LOD as the outcome. LBP cases with at least 1 day of work disability were identified by reviewing indemnity service records and medical bills using a comprehensive list of codes from the International Classification of Diseases, Ninth Edition (ICD-9) indicating LBP or nonspecific back pain, excluding medically complicated cases. RESULTS: We found significant between-state variations in the negative impact of eMRI on LOD ranging from 3.4 days in Tennessee to 14.8 days in New Hampshire. Higher negative impact of eMRI on LOD was mainly associated with female gender, state workers' compensation (WC) policy not limiting initial treating provider choice, higher state orthopedic surgeon density, and lower state MRI facility density. CONCLUSION: State WC policies regulating selection of healthcare provider and structural factors affecting quality of medical care modify the impact of eMRI not adherent to guidelines. Targeted healthcare and work disability prevention interventions may improve work disability outcomes in patients with occupational LBP.

Basal Sodium-Dependent Vitamin C Transporter 2 polarization in choroid plexus explant cells in normal or scorbutic conditions.

Vitamin C is incorporated into the cerebrospinal fluid (CSF) through choroid plexus cells. While the transfer of vitamin C from the blood to the brain has been studied functionally, the vitamin C transporter, SVCT2, has not been detected in the basolateral membrane of choroid plexus cells. Furthermore, it is unknown how its expression is induced in the developing brain and modulated in scurvy conditions. We concluded that SVCT2 is intensely expressed in the second half of embryonic brain development and postnatal stages. In postnatal and adult brain, SVCT2 is highly expressed in all choroidal plexus epithelial cells, shown by colocalization with GLUT1 in the basolateral membranes and without MCT1 colocalization, which is expressed in the apical membrane. We confirmed that choroid plexus explant cells (in vitro) form a sealed epithelial structure, which polarized basolaterally, endogenous or overexpressed SVCT2. These results are reproduced in vivo by injecting hSVCT2wt-EYFP lentivirus into the CSF. Overexpressed SVCT2 incorporates AA (intraperitoneally injected) from the blood to the CSF. Finally, we observed in Guinea pig brain under scorbutic condition, that normal distribution of SVCT2 in choroid plexus may be regulated by peripheral concentrations of vitamin C. Additionally, we observed that SVCT2 polarization also depends on the metabolic stage of the choroid plexus cells.

Whole-body vibration and back pain-related work absence among heavy equipment vehicle mining operators.

OBJECTIVE: To determine the association between several whole-body vibration (WBV) exposure estimates and back pain-related work absence. METHODS: Exposures (based on the weighted daily root mean square acceleration, A(8); the daily vibration dose value, VDV(8); and the daily equivalent static compression dose, Sed(8)) of 2302 workers during 4 years were estimated using each worker's monthly vehicle operation records and WBV measurements from 11 different types of heavy equipment vehicles in a large coal mine. Company payroll data provided work absence during the concurrent 4 years of exposure. Cox regression models estimated the associations between the different WBV metrics and time to first work absence related to back pain. An adjusted R2 statistic provided a measure of model fit. RESULTS: All estimated metrics of WBV exposures were positively and significantly associated with back pain-related absence. HRs varied from 2.03 to 12.39 for every 0.21 m/s2 increase in the A(8)-based exposures; from 1.03 to 1.18 for every 1.72 m/s1.75 increase in VDV(8)-based exposures; and from 1.04 to 1.07 for every 0.06 MPa increase in Sed(8)-based exposures. Models using the estimated VDV(8) metric for the z axis fit the data best as measured by the R2 statistic. CONCLUSION: Higher WBV exposures were associated with back pain-related absences in this population, which appears after a few years of follow-up. Introducing controls to lower exposure levels may help reduce back pain-related work absences.

The median eminence as the hypothalamic area involved in rapid transfer of glucose to the brain: functional and cellular mechanisms.

Our data proposes that glucose is transferred directly to the cerebrospinal fluid (CSF) of the hypothalamic ventricular cavity through a rapid "fast-track-type mechanism" that would efficiently stimulate the glucosensing areas. This mechanism would occur at the level of the median eminence (ME), a periventricular hypothalamic zone with no blood-brain barrier. This "fast-track" mechanism would involve specific glial cells of the ME known as ß2 tanycytes that could function as "inverted enterocytes," expressing low-affinity glucose transporters GLUT2 and GLUT6 in order to rapidly transfer glucose to the CSF. Due to the large size of tanycytes, the presence of a high concentration of mitochondria and the expression of low-affinity glucose transporters, it would be expected that these cells accumulate glucose in the endoplasmic reticulum (ER) by sequestering glucose-6-phosphate (G-6-P), in a similar way to that recently demonstrated in astrocytes. Glucose could diffuse through the cells by micrometric distances to be released in the apical region of ß2 tanycytes, towards the CSF. Through this mechanism, levels of glucose would increase inside the hypothalamus, stimulating glucosensing mechanisms quickly and efficiently. KEY MESSAGES: • Glucose diffuses through the median eminence cells (ß2 tanycytes), towards the hypothalamic CSF. • Glucose is transferred through a rapid "fast-track-type mechanism" via GLUT2 and GLUT6. • Through this mechanism, hypothalamic glucose levels increase, stimulating glucosensing.

The Association of Occupational Psychosocial Factors with the Prevalence of Irritable Bowel Syndrome in the Chilean Working Population.

BACKGROUND: Irritable bowel syndrome (IBS) is a stress-related disease linked to psychosocial factors, though knowledge about its occupational psychosocial aspects is scarce. OBJECTIVE: A cross-sectional study of the prevalence of IBS and its association with occupational psychosocial factors in Chilean workers was conducted. METHODS: IBS prevalence, using the IBS-Rome IV criteria, in the working population was estimated using data from the National Health Survey of 2009. Data on occupational psychosocial aspects were drawn from the Chilean Survey of Employment, Health, and Work of 2009, and allocated to individual survey participants at the occupation-region level. Data on family and community stressors were available at the individual level. Prevalence ratios (PR) for IBS were computed using generalized linear mixed models to account for variability at the group level. RESULTS: The IBS prevalence in the overall working population (weighted n = 5 435 253) was 18.4%, but varied substantially by industry sector. Compared with 'professionals' (IBS prevalence = 7.3%), jobs with high prevalence of IBS included 'health and social work activities' [PR = 4.9; 95% confidence interval (CI) = 1.4-16.7], 'household employment' (PR = 4.8; 95% CI = 1.5-15.9), and 'manufacturing' (PR = 3.5; 95% CI = 1.0-11.8). With Karasek Job Demand Control scores assigned to occupations within regions, high job demand doubled the prevalence of IBS (PR = 2.0; 95% CI = 1.4-2.9), whereas high-skill discretion was associated with lower prevalence of IBS (PR = 0.6; 95% CI = 0.4-0.8). There was also evidence that these two factors were not independent; high-skill discretion appeared to buffer the effect of high job demand on IBS prevalence (P < 0.001). CONCLUSIONS: Occupational factors were associated with IBS prevalence, showing effects as important as those for non-occupational stresses such as civic insecurity or having health problems. High job skill discretion appeared to reduce the prevalence of IBS in the presence of high job demands. Given its high overall prevalence and poorly understood risk factors, further research on occupational psychosocial factors of IBS is warranted.

Chronic In Vivo Effects of Repeated Exposure to Low Oral Doses of Tetrodotoxin: Preliminary Evidence of Nephrotoxicity and Cardiotoxicity.

Tetrodotoxin (TTX) is one of the most potent naturally occurring neurotoxins. InitiallyTTX was associated with human food intoxications in Japan, but nowadays, concerns about thehuman health risks posed by TTX have increased in Europe after the identification of the toxin infish, marine gastropods, and bivalves captured in European waters. Even when TTX monitoring isnot currently performed in Europe, an acute oral no observable effect level (NOAEL) of 75 µg/kghas been recently established but, to date, no studies evaluating the chronic oral toxicity of TTXhave been released, even when EFSA has highlighted the need for them. Thus, in this work, thechronic effects of low oral TTX doses (below the acute lethal dose 50) were evaluated followinginternationally adopted guidelines. The results presented here demonstrate that low oral doses ofTTX have deleterious effects on renal and cardiac tissues. Moreover, alterations in bloodbiochemistry parameters, urine production, and urinalysis data were already detected at the oraldose of 75 µg/kg after the 28 days exposure. Thus, the data presented here constitute an initialapproach for the chronic evaluation of the in vivo toxicity of tetrodotoxin after its ingestion throughcontaminated fishery products.