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Inward rectifying potassium channels (Kir) are a large family of ion channels that play key roles in ion homeostasis in oligodendrocytes, the myelinating cells of the central nervous system (CNS). Prominent expression of Kir4.1 has been indicated in oligodendrocytes, but the extent of expression of other Kir subtypes is unclear. Here, we used qRT-PCR to determine expression of Kir channel transcripts in the mouse optic nerve, a white matter tract comprising myelinated axons and the glia that support them. A novel finding was the high relative expression of Kir7.1, comparable to that of Kir4.1, the main glial Kir channel. Significantly, Kir7.1 immunofluorescence labelling in optic nerve sections and in isolated cells was localised to oligodendrocyte somata. Kir7.1 are known as a K+transporting channels and, using patch clamp electrophysiology and the Kir7.1 blocker VU590, we demonstrated Kir7.1 channels carry a significant proportion of the whole cell potassium conductance in oligodendrocytes isolated from mouse optic nerves. Notably, oligodendrocytes are highly susceptible to ischemia/hypoxia and this is due at least in part to disruption of ion homeostasis. A key finding of this study is that blockade of Kir7.1 with VU590 compromised oligodendrocyte cell integrity and compounds oligodendroglial loss in ischemia/hypoxia in the oxygen–glucose deprivation (OGD) model in isolated intact optic nerves. These data reveal Kir7.1 channels are molecularly and functionally expressed in oligodendrocytes and play an important role in determining oligodendrocyte survival and myelin integrity.

An alternative instructional model, which due to the social reality created by the ongoing COVID-19 pandemic is gaining more and more popularity in the global educational community, is the so called “flipped classroom”. In this paper we give the details of a one-week qualitative research we conducted in order to explore the effectiveness of the flipped classroom model in an undergraduate “mathematics education” course in Greece. The study involved thirty third-year math students, whose achievements and perceptions were captured with the help of questionnaire, task, personal interviews, and open discussion in the class. The analysis of the research data indicated increased engagement of the students, development of positive attitudes about the learning, control of the learning pace, autonomy in managing the time required for study and relative improvement of students’ performance in problem solving and teamwork. At the same time, several challenges emerged. The main ones concerned the demand for frequent active students’ participation in the educational process, the management of queries during the homework, the doubts about the effectiveness of the method on difficult teaching subjects, as well as the time and skill requirements for preparing such a lesson.

The National Health Service (NHS) epidermolysis bullosa (EB) service, established in 2002, offers comprehensive, free care to all patients in England and Wales.To quantify prevalence, incidence and mortality of EB in England and Wales.Demographic data for patients in England and Wales were collected on a secure electronic database, prospectively from January 2002 to April 2021 and retrospectively for cases prior to 2002. Vital status was verified using central NHS data.By March 2021, 2594 individuals were registered, of whom 2361 were living, which yielded a prevalence of 34·8 per million of the population for all EB types [EB simplex (EBS) 17 per million, dystrophic EB (DEB) 10·7 per million, junctional EB (JEB) 1 per million and Kindler EB 0·3 per million]. We recorded 1200 babies with EB born since 2002. The average incidence per million live births for EBS, DEB, JEB and Kindler EB was 32·5, 26·1, 8·9 and 0·9, respectively (total incidence for all types of EB was 67·8 per million). Birth rates fell progressively over the 19-year period for JEB-severe (JEB-S) (r = -0·56) and recessive DEB-severe (r = -0·44) and also for milder types of EB. We observed longer survival in JEB-S over the 19-year period (rIn this study, we provide the first accurate epidemiological data for EB in England and Wales. We believe the observed reduction in birth incidence of severe types of EB reflects an uptake of genetic counselling advice, whereas the reduction in milder types may be due to delayed presentation. A potential small trend towards longer survival of babies with JEB-S may reflect improved multidisciplinary care.

Ο θόρυβος έχει αναδειχθεί σ’ έναν από τους σημαντικότερους παράγοντες υποβάθμισης του περιβάλλοντος και κατ’ επέκταση της ποιότητας της ζωής μας. Αποτελεί μια ‘αόρατη’ απειλή, την οποία δεν βλέπουμε, όμως τη βιώνουμε καθημερινά. Ο Παγκόσμιος Οργανισμός Υγείας θεωρεί ότι η ηχορύπανση έρχεται δεύτερη στην κατάταξη των περιβαλλοντικών κινδύνων για την υγεία. Μελέτες δείχνουν ότι το πρόβλημα του θορύβου βρίσκεται σε συνάρτηση με την πυκνότητα του πληθυσμού (WHO,1999).Τα παιδιά ανήκουν στις ευαίσθητές ομάδες όπου οι επιπτώσεις του θορύβου στην υγεία τους είναι ζημιογόνες. Αυτό γίνεται αντιληπτό ιδιαίτερα στα σχολεία που βρίσκονται στα μεγάλα αστικά κέντρα, όπου εκεί τα παιδιά εκτίθενται σε πολλές και ανεξέλεγκτες πηγές θορύβου (Shied&Dockrell,2004).Η παρούσα μελέτη είχε ως στόχο την διερεύνηση της επίδρασης του περιβαλλοντικού θορύβου στην επίδοση των μαθητών σε γνωστική δοκιμασία-τεστ γλώσσας και μαθηματικών. Προσδιορίστηκαν οι συχνότεροι τύποι εξωτερικού και εσωτερικού θορύβου στα σχολεία τριών διαφορετικών σε μέγεθος πόλεων και διερευνήθηκε ο βαθμός στον οποίο τα παιδιά αντιλαμβάνονται το θόρυβο ως ενόχληση στη διάρκεια του μαθήματος σε σχέση και με την ευρύτερη περιοχή του σχολείου (διαφοροποίηση ανά πόλη). Διερεύνησε το βαθμό ενόχλησης των παιδιών από τους εξωτερικούς και τους εσωτερικούς θόρυβο κατά την ώρα του μαθήματος.5Τα αποτελέσματα επιβεβαιώνουν τη σημασία των θορύβων ιδιαίτερα δε των εξωτερικών στην επίδοση των παιδιών στο δημοτικό σχολείο και ειδικά στις δοκιμασίες ανάγνωσης. Διαπιστώθηκε ότι οι επιπτώσεις του θορύβου έχουν διαφορετική βαρύτητα σε αγόρια και κορίτσια και επηρεάζουν σε διαφορετικό βαθμό διαφορετικές γνωστικές διεργασίες. Τα κορίτσια και στα τρία επίπεδα θορύβου (χαμηλό, μέτριο, υψηλό επίπεδο) είχαν καλύτερες επιδόσεις από τα αγόρια στη γλώσσα. Στη συνολική βαθμολογία των μαθητών διαπιστώθηκε στατιστικά σημαντική διαφορά στα σχολεία υψηλού θορύβου έναντι των υπολοίπων, τόσο όσον αφορά τη γλώσσα, όσο και τη συνολική βαθμολογία. Στα μαθηματικά δεν υπήρξε στατιστικά σημαντική διαφορά. Τέλος όταν το επίπεδο του θορύβου είναι υψηλό, η ολοκλήρωση ασκήσεων υπολείπεται με στατιστικά σημαντική διαφορά απ΄ ότι σε χαμηλό και μέτριο θόρυβο

The field of cannabinoid research has been receiving ever-growing interest. Ongoing debates worldwide about the legislation of medical cannabis further motivates research into cannabinoid function within the central nervous system (CNS). To date, two well-characterized cannabinoid receptors exist. While most research has investigated Cb

Ketogenic diets are effective therapies for refractory epilepsy, yet the underlying mechanisms are incompletely understood. The anticonvulsant efficacy of ketogenic diets correlates positively to the serum concentration of β-hydroxybutyrate (BHB), the primary ketone body generated by ketosis. Voltage-gated potassium channels generated by KCNQ2-5 subunits, especially KCNQ2/3 heteromers, generate the M-current, a therapeutic target for synthetic anticonvulsants. Here, we report that BHB directly activates KCNQ2/3 channels (EC50 = 0.7 µM), via a highly conserved S5 tryptophan (W265) on KCNQ3. BHB was also acutely effective as an anticonvulsant in the pentylene tetrazole (PTZ) seizure assay in mice. Strikingly, coadministration of γ-amino-β-hydroxybutyric acid, a high-affinity KCNQ2/3 partial agonist that also acts via KCNQ3-W265, similarly reduced the efficacy of BHB in KCNQ2/3 channel activation in vitro and in the PTZ seizure assay in vivo. Our results uncover a novel, unexpected molecular basis for anticonvulsant effects of the major ketone body induced by ketosis. SIGNIFICANCE STATEMENT: Ketogenic diets are used to treat refractory epilepsy but the therapeutic mechanism is not fully understood. Here, we show that clinically relevant concentrations of β-hydroxybutyrate, the primary ketone body generated during ketogenesis, activates KCNQ2/3 potassium channels by binding to a specific site on KCNQ3, an effect known to reduce neuronal excitability. We provide evidence using a mouse chemoconvulsant model that KCNQ2/3 activation contributes to the antiepileptic action of β-hydroxybutyrate.

Transmembrane channel-like protein isoform 1 (TMC1) is essential for the generation of mechano-electrical transducer currents in hair cells of the inner ear. TMC1 disruption causes hair cell degeneration and deafness in mice and humans. Although thought to be expressed at the cell surface in vivo, TMC1 remains in the endoplasmic reticulum when heterologously expressed in standard cell lines, precluding determination of its roles in mechanosensing and pore formation. Here, we report that the KCNQ1 Kv channel forms complexes with TMC1 and rescues its surface expression when coexpressed in Chinese Hamster Ovary cells. TMC1 rescue is specific for KCNQ1 within the KCNQ family, is prevented by a KCNQ1 trafficking-deficient mutation, and is influenced by KCNE β subunits and inhibition of KCNQ1 endocytosis. TMC1 lowers KCNQ1 and KCNQ1-KCNE1 K+ currents, and despite the surface expression, it does not detectably respond to mechanical stimulation or high salt. We conclude that TMC1 is not intrinsically mechano- or osmosensitive but has the capacity for cell surface expression, and requires partner protein(s) for surface expression and mechanosensitivity. We suggest that KCNQ1, expression of which is not thought to overlap with TMC1 in hair cells, is a proxy partner bearing structural elements or a sequence motif reminiscent of a true in vivo TMC1 hair cell partner. Discovery of the first reported strategy to rescue TMC1 surface expression should aid future studies of the TMC1 function and native partners.

Voltage-gated potassium (Kv) channels are a family of membrane proteins that facilitate K+ ion diffusion across the plasma membrane, regulating both resting and action potentials. Kv channels comprise four pore-forming α subunits, each with a voltage sensing domain, and they are regulated by interaction with β subunits such as those belonging to the KCNE family. Here we conducted a comprehensive biophysical characterization of stoichiometry and protein diffusion across the plasma membrane of the epithelial KCNQ1-KCNE2 complex, combining total internal reflection fluorescence (TIRF) microscopy and a series of complementary Fluorescence Fluctuation Spectroscopy (FFS) techniques. Using this approach, we found that KCNQ1-KCNE2 has a predominant 4:4 stoichiometry, while non-bound KCNE2 subunits are mostly present as dimers in the plasma membrane. At the same time, we identified unique spatio-temporal diffusion modalities and nano-environment organization for each channel subunit. These findings improve our understanding of KCNQ1-KCNE2 channel function and suggest strategies for elucidating the subunit stoichiometry and forces directing localization and diffusion of ion channel complexes in general.

Epidermolysis bullosa (EB) is a highly diverse group of inherited skin disorders, resulting from mutations in genes encoding proteins of the dermal-epidermal junction (DEJ). Itch (pruritus) is one of the commonest symptoms across all EB subtypes. It occurs in blistered or wounded sites, or manifests as a generalized phenomenon, thereby affecting both intact skin and healing wounds. The mechanism of pruritus in EB is unclear. It is likely that skin inflammation secondary to barrier disruption, wound healing cascades and dysregulated activation of epidermal sensory nerve endings are all involved in its pathophysiology on the molecular and cellular level. Understanding these mechanisms in depth is crucial in developing optimised treatments for people with EB and improving quality of life. This review summarises current evidence on the prevalence, mechanisms and management of itch in EB.

There is increasing evidence that myelin disruption is related to cognitive decline in Alzheimer's disease (AD). In the CNS, myelin is produced by oligodendrocytes, which are generated throughout life by adult oligodendrocyte progenitor cells (OPCs), also known as NG2-glia. To address whether alterations in myelination are related to age-dependent changes in OPCs, we analyzed NG2 and myelin basic protein (MBP) immunolabelling in the hippocampus of 3×Tg-AD mice at 6 and 24 months of age, compared with non-Tg age-matched controls. There was an age-related decrease in MBP immunostaining and OPC density, together with a decline in the number of OPC sister cells, a measure of OPC replication. Notably, the loss of myelin and OPC sister cells occurred earlier at 6 months in 3xTg-AD, suggesting accelerated aging, although there was not a concomitant decline in OPC numbers at this age, suggesting the observed changes in myelin were not a consequence of replicative exhaustion, but possibly of OPC disruption or senescence. In line with this, a key finding is that compared to age-match controls, OPC displayed marked morphological atrophy at 6 months in 3xTg-AD followed by morphological hypertrophy at 24 months, as deduced from significant changes in total cell surface area, total cell volume, somata volume and branching of main processes. Moreover, we show that hypertrophic OPCs surround and infiltrate amyloid-β (Aβ) plaques, a key pathological hallmark of AD. The results indicate that OPCs undergo complex age-related remodeling in the hippocampus of the 3xTg-AD mouse model. We conclude that OPC disruption is an early pathological sign in AD and is a potential factor in accelerated myelin loss and cognitive decline., Graphical abstract, Highlights • Life-long generation of myelin is the function of adult oligodendrocyte progenitor cells (OPCs). • Age-related loss of myelin is accelerated in the 3xTg-AD mouse model of Alzheimer's disease (AD). • OPCs are disrupted at an early stage of 3xTg-AD. • Dysregulation of OPC and myelin loss are important biomarkers for AD-like pathology.

New affordances for online discussion forums are increasingly explored. In this regard, gamification elements such as badges, progress bars and progress visualizations are used in order to increase students' engagement and participation. This study uses the Community of Inquiry model to explore students' critical thinking under the effect of a) a community and b) individual gamification elements, over two discussions. Reaching the last discussion of the course, the students, who were awarded individual gamification elements, attained higher levels of critical thinking compared to the students that were awarded community gamification elements. Teaching presence has been influenced by the gamification elements provided, regardless of their type. The results highlight the value of gamification on the student's conscious awareness of their own thinking and learning.

Purpose This study aims at identifying the sex-stratified associations of involvement in traditional bullying during middle and high school years and in cyberbullying during college years with multiple health risk behaviors in undergraduate students. Design This cross-sectional analysis draws on the data of the second wave of the LATO study (Lifestyle & Attitudes in a Student Population) in Greece. Methods During November and December 2013, 812 second-year undergraduate students (mean age = 19.3 years; girls = 66.1%) provided data on substance use (smoking, alcohol abuse or drunkenness, illegal drug use including marijuana, hashish, and cannabis) and sexual risk taking (paying for sex and not using condoms) and completed the Cyberbullying and its Effects and the Retrospective Bullying Questionnaires. Logistic regression models performed were adjusted for potential confounders. Findings Both male and female late adolescents who were victims of bullying during middle and high school were less likely to use condoms during college years when compared to uninvolved students. Among males, being a bully or victim at school doubled the odds for past month drunkenness and tripled the odds of paying for sex. Greater likelihood to pay for sex was also evident in bullying victims. Cyberbully or cybervictim male students were more likely to report smoking. In female bullying victims, alcohol abuse associations were somewhat conflicting, with decreased lifetime but increased past month likelihood for drunkenness. Conclusions Engagement in bullying and cyberbullying is associated with the manifestation of gender-specific health risk behaviors for the different involvement groups in college students. Clinical Relevance Involvement in bullying and cyberbullying is a major public health concern due to the associations with multiple health risk behaviors. Nurses and healthcare professionals should adopt multifaceted prevention interventions tailored according to bullying status and gender that extend through all educational levels.

Inward Rectifying Potassium channels (Kir) are a large family of ion channels that play key roles in ion homeostasis and neuronal excitability. The most recently described Kir subtype is Kir7.1, which is known as a K+ transporting subtype. Earlier studies localised Kir7.1 to subpopulations of neurones in the brain. However, the pattern of Kir7.1 expression across the brain has not previously been examined. Here, we have determined neuronal and glial expression of Kir7.1 in the adult mouse brain, using immunohistochemistry and transgenic mouse lines expressing reporters specific for astrocytes [glial fibrillary acidic protein‐enhanced green fluorescent protein (GFAP‐EGFP], myelinating oligodendrocytes (PLP‐DsRed), oligodendrocyte progenitor cells (OPC, Pdgfra‐creERT2/Rosa26‐YFP double‐transgenic mice) and all oligodendrocyte lineage cells (SOX10‐EGFP). The results demonstrate significant neuronal Kir7.1 immunostaining in the cortex, hippocampus, cerebellum and pons, as well as the striatum and hypothalamus. In addition, astrocytes are shown to be immunopositive for Kir7.1 throughout grey and white matter, with dense immunostaining on cell somata, primary processes and perivascular end‐feet. Immunostaining for Kir7.1 was observed in oligodendrocytes, myelin and OPCs throughout the brain, although immunostaining was heterogeneous. Neuronal and glial expression of Kir7.1 is confirmed using neurone‐glial cortical cultures and optic nerve glial cultures. Notably, Kir7.1 have been shown to regulate the excitability of thalamic neurones and our results indicate this may be a widespread function of Kir7.1 in neurones throughout the brain. Moreover, based on the function of Kir7.1 in multiple transporting epithelia, Kir7.1 are likely to play an equivalent role in the primary glial function of K+ homeostasis. Our results indicate Kir7.1 are far more pervasive in the brain than previously recognised and have potential importance in regulating neuronal and glial function.

Oligodendrocytes are the myelinating cells of the CNS, producing the insulating myelin sheath that facilitates rapid electrical conduction of axonal action potentials. Oligodendrocytes arise from oligodendrocyte progenitor cells (OPCs) under the control of multiple factors, including neurotransmitters and other neuron-derived factors. A significant population of OPCs persists in the adult CNS, where they are often referred to as NG2-glia, because they are identified by their expression of the NG2 chondroitin sulphate proteoglycan (CSPG4). In the adult brain, the primary function of NG2-glia is the life-long generation of oligodendrocytes to replace myelin lost through natural 'wear and tear' and pathology, as well as to provide new oligodendrocytes to myelinate new connections formed in response to new life experiences. NG2-glia contact synapses and respond to neurotransmitters and potassium released during neuronal transmission; to this end, NG2-glia (OPCs) express multiple neurotransmitter receptors and ion channels, with prominent roles being identified for glutamatergic signalling and potassium channels in oligodendrocyte differentiation. Myelinating oligodendrocytes also express a wide range of neurotransmitter receptors and ion channels, together with transporters and gap junctions; together, these have critical functions in cellular ion and water homeostasis, as well as metabolism, which is essential for maintaining myelin and axon integrity. An overriding theme is that oligodendrocyte function and myelination is not only essential for rapid axonal conduction, but is essential for learning and the long-term integrity of axons and neurones. Hence, myelination underpins cognitive function and the massive computing power of the human brain and myelin loss has devastating effects on CNS function. This chapter focuses on normal oligodendrocyte physiology.

Oligodendrocytes are the myelinating cells of the CNS, producing the insulating myelin sheath that facilitates rapid electrical conduction of axonal action potentials. Oligodendrocytes arise from oligodendrocyte progenitor cells (OPCs) under the control of multiple factors, including neurotransmitters and other neuron-derived factors. A significant population of OPCs persists in the adult CNS, where they are often referred to as NG2-glia, because they are identified by their expression of the NG2 chondroitin sulphate proteoglycan (CSPG4). In the adult brain, the primary function of NG2-glia is the life-long generation of oligodendrocytes to replace myelin lost through natural 'wear and tear' and pathology, as well as to provide new oligodendrocytes to myelinate new connections formed in response to new life experiences. NG2-glia contact synapses and respond to neurotransmitters and potassium released during neuronal transmission; to this end, NG2-glia (OPCs) express multiple neurotransmitter receptors and ion channels, with prominent roles being identified for glutamatergic signalling and potassium channels in oligodendrocyte differentiation. Myelinating oligodendrocytes also express a wide range of neurotransmitter receptors and ion channels, together with transporters and gap junctions; together, these have critical functions in cellular ion and water homeostasis, as well as metabolism, which is essential for maintaining myelin and axon integrity. An overriding theme is that oligodendrocyte function and myelination is not only essential for rapid axonal conduction, but is essential for learning and the long-term integrity of axons and neurones. Hence, myelination underpins cognitive function and the massive computing power of the human brain and myelin loss has devastating effects on CNS function. This chapter focuses on normal oligodendrocyte physiology.

Gastrointestinal (GI) motility disorders such as irritable bowel syndrome (IBS) can occur when coordinated smooth muscle contractility is disrupted. Potassium (K+) channels regulate GI smooth muscle tone and are key to GI tract relaxation, but their molecular and functional phenotypes are poorly described. Here we define the expression and functional roles of mechano-gated K2P channels in mouse ileum and colon. Expression and distribution of the K2P channel family were investigated using quantitative RT-PCR (qPCR), immunohistochemistry and confocal microscopy. The contribution of mechano-gated K2P channels to mouse intestinal muscle tension was studied pharmacologically using organ bath. Multiple K2P gene transcripts were detected in mouse ileum and colon whole tissue preparations. Immunohistochemistry confirmed TREK-1 expression was smooth muscle specific in both ileum and colon, whereas TREK-2 and TRAAK channels were detected in enteric neurons but not smooth muscle. In organ bath, mechano-gated K2P channel activators (Riluzole, BL-1249, flufenamic acid, and cinnamyl 1-3,4-dihydroxy-alpha-cyanocinnamate) induced relaxation of KCl and CCh pre-contracted ileum and colon tissues and reduced the amplitude of spontaneous contractions. These data reveal the specific expression of mechano-gated K2P channels in mouse ileum and colon tissues and highlight TREK-1, a smooth muscle specific K2P channel in GI tract, as a potential therapeutic target for combating motility pathologies arising from hyper-contractility.

The objective of the present study was the quantitative assessment of the previously documented inverse relationship between Alzheimer's Disease (AD) and cancer (CA) by conducting a meta-analysis and evaluating systematic differentiations of the aforementioned relationship based on cancer localization. For the purpose of the study all available empirical data of the last decade, which met specific criteria, were included in the analysis by querying PubMed, Web of Science and Cochrane Library databases. Seven studies were included in the analysis, with a total sample of 18,887 (10,859 AD patients, 8,028 non-demented controls) participants to calculate cancer risk among AD patients, and 11 studies, with a total of 5,607,076 (1,853,318 cancer patients, 3,753,758 healthy controls) participants, were assessed to evaluate AD risk among cancer patients. The analysis revealed that AD patients appear to have a reduced risk of cancer, by 40% (RR 0.60, 95% CI 0.45 - 0.79), while cancer history was associated with a reduced risk of AD, by 15% (RR 0.85, 95% CI 0.77-0.92). Systematic differences were also identified based on site-specific cancer. Indications of heterogeneity and publication bias were present in the analysis. Our meta-analysis is only the fourth conducted on this subject, with newer evidence suggesting a mitigation of the inverse relationship. We emphasize the need for new studies to assess the inverse comorbidity hypothesis, especially in AD patients.

Studies by Bruce Ransom and colleagues have made a major contribution to show that white matter is susceptible to ischemia/hypoxia. White matter contains axons and the glia that support them, notably myelinating oligodendrocytes, which are highly vulnerable to ischemic-hypoxic damage. Previous studies have shown that metabotropic GluRs (mGluRs) are cytoprotective for oligodendrocyte precursor cells and immature oligodendrocytes, but their potential role in adult white matter was unresolved. Here, we report that group 1 mGluR1/5 and group 2 mGluR3 subunits are expressed in optic nerves from mice aged postnatal day (P)8–12 and P30–35. We demonstrate that activation of group 1 mGluR protects oligodendrocytes against oxygen-glucose deprivation (OGD) in developing and young adult optic nerves. In contrast, group 2 mGluR are shown to be protective for oligodendrocytes against OGD in postnatal but not young adult optic nerves. The cytoprotective effect of group 1 mGluR requires activation of PKC, whilst group 2 mGluR are dependent on negatively regulating adenylyl cyclase and cAMP. Our results identify a role for mGluR in limiting injury of oligodendrocytes in developing and young adult white matter, which may be useful for protecting oligodendrocytes in neuropathologies involving excitoxicity and ischemia/hypoxia.

This study aims at identifying the sex-stratified associations of involvement in traditional bullying during middle and high school years and in cyberbullying during college years with multiple health risk behaviors in undergraduate students.This cross-sectional analysis draws on the data of the second wave of the LATO study (LifestyleAttitudes in a Student Population) in Greece.During November and December 2013, 812 second-year undergraduate students (mean age = 19.3 years; girls = 66.1%) provided data on substance use (smoking, alcohol abuse or drunkenness, illegal drug use including marijuana, hashish, and cannabis) and sexual risk taking (paying for sex and not using condoms) and completed the Cyberbullying and its Effects and the Retrospective Bullying Questionnaires. Logistic regression models performed were adjusted for potential confounders.Both male and female late adolescents who were victims of bullying during middle and high school were less likely to use condoms during college years when compared to uninvolved students. Among males, being a bully or victim at school doubled the odds for past month drunkenness and tripled the odds of paying for sex. Greater likelihood to pay for sex was also evident in bullying victims. Cyberbully or cybervictim male students were more likely to report smoking. In female bullying victims, alcohol abuse associations were somewhat conflicting, with decreased lifetime but increased past month likelihood for drunkenness.Engagement in bullying and cyberbullying is associated with the manifestation of gender-specific health risk behaviors for the different involvement groups in college students.Involvement in bullying and cyberbullying is a major public health concern due to the associations with multiple health risk behaviors. Nurses and healthcare professionals should adopt multifaceted prevention interventions tailored according to bullying status and gender that extend through all educational levels.

White matter (WM) tracts contain bundles of myelinated axons and the glia that support them, namely oligodendrocytes that form the myelin and astrocytes, which provide structural and homeostatic support, together with small populations of microglia and oligodendrocyte precursor cells. Neurotransmitter signaling is prominent in WM, and there is a significant role for adrenergic signaling, together with glutamatergic and purinergic mechanisms. The site of axoglial signaling in myelinated axons is the node of Ranvier, which is the site of action potential propagation and displays many properties of synapses. Neurotransmitters released during axonal electrical activity activate receptors on perinodal astrocytes, to stimulate their release of gliotransmitters that integrate function within axon–glial–vascular networks. One of the key functions of astroglial adrenergic signaling in WM is to maintain energy supply to axons and oligodendrocytes, ensuring efficient and rapid information transfer throughout the central nervous system and maintaining WM integrity in times of energy stress.

Background Both bullying and cyber bullying have a long-term negative impact on mental health and social life that extends to adulthood. However, their possible associations with multiple health risk behaviours have not been explored yet. This study aims to explore the exposure of students to bullying through the six secondary education years and its associations with cyber-bullying and nine health risk behaviours during university years. Methods …

Tucked away in a corner of the editor's commentary page in the August 1919 issue of The Play Pictorial is an advertisement that promises a simple cure for an actress's possible bad luck in getting her break I having a successful stage career: improve personality, To do this, one only needed to get a book ("which every artiste should send for immediately") promoting the Kallone Course, a class that could teach every woman interested in a stage career how "this 'asset' [personality] can really be acquired."

Throughout the course of modern history, coasts have been a substantial means of human development and an ever-growing number of people still continue to colonize the coasts worldwide. Coasts comprise dynamic and complex socio-ecological systems, encompassing a variety of biotic and abiotic elements. Their complexity and dynamics are reflected in the multiplicity of their forms. Their dynamic nature is responsible for their high productivity, leading both to periodic changes and gradual mutation. The marine ecosystems, by storing carbon dioxide and by releasing oxygen to the atmosphere through the living processes of the phytoplankton population, play a significant role in regulating climate. The coastal areas help create and preserve microclimates. The existence of coastal forests and wetlands ensures minimization of floods, erosion and other natural disasters, and offers valuable regulating and supporting ecosystem services. The importance of coastal resources for the prosperity of coastal areas can be specified through the ecosystem services and goods, which support the human life (Daily, 1997; Turner et al., 2001; Beaumont, 2007; Kontogianni et al., 2010a). The categorization of coastal services and goods is presented in Table 1. However, the ensuing anthropogenic activities of industrialization and economic growth have brought the coastal areas under intense pressure. Climatic change accentuates these pressures while it makes mean sea level rise (SLR) one of the most predictable and alarming impacts globally (Church et al., 2001; Nicholls, 2007). To make things worse, SLR is known to be rather inelastic against the reduction of greenhouse gas emissions (OECD, 2006), a phenomenon known as “commitment to SLR”. That is, even if drastic reduction policies globally succeed in stabilizing the climate, SLR and the accompanying phenomena of coastal erosion and storm surges will continue to occur for centuries (Meehl et al., 2005; Wigley, 2005), causing possible tipping points for some systems (Tipping Points Report, 2009). This chapter examines the impacts of SLR on the Greek coastal zone and appraises their economic dimension. Researchers engaged in studies like this face two important issues. The first is the quantification of the economic impacts (damages) caused by the losses of coastal areas due to SLR. The second is the ex ante estimation of welfare gains from reducing SLR risks, since this estimation constitutes an important input for decision-making regarding

Background/Aims In patients with gastroesophageal reflux disease, persistent symptoms on proton pump inhibitor (PPI) therapy may be due to residual acid or non-acid reflux. Combined impedance-pH has been suggested to be superior to pH alone in the management of refractory patients to PPI. The utility of implementation of this technique in every day clinical practice is still unknown. The aim of this study was to investigate the outcomes of patients studied with combined impedance-pH and to evaluate the yield of additional impedance monitoring over pH alone in patients with persistent gastroesophageal reflux disease symptoms. Methods Seventy-one patients (31 men; mean age, 49.1 +/- 15.5 years) on PPI therapy underwent combined impedance-pH for persistent typical (76%) or atypical (49%) symptoms. Results During impedance-pH study, 44 (62%) patients reported symptoms. A positive symptom index (SI) was found in 21(48%) patients: 8 (18.2%) had a positive SI for acid reflux, 9 (20.5%) for non-acid reflux and 4 (9.1%) for mixed reflux. Addition of impedance allowed association between reflux and symptoms in 20.5% of patients who would have been missed by pH study alone. Heartburn was the most prevalent symptom associated with acid reflux, whereas regurgitation and ear, nose and throat symptoms were associated with non-acid reflux. Conclusions The use of combined impedance-pH monitoring substantially increased the diagnostic yield compared to pH alone. With SI analysis, 20.5% of patients received a diagnosis that could not have been achieved with pH testing alone.

Interrupted inferior vena cava (IVC) is a rare congenital abnormality often combined with cardiovascular and visceral malformations. We report the case of a 63-year-old male who presented in complete heart block with periodic absence of an escape rhythm requiring emergency temporary pacing. The trans-femoral …

Mutations in the lipoprotein lipase (LPL) gene are the most common cause of familial chylomicronemia. Here we define the molecular basis of LPL deficiency in four patients of German, French, Dutch, and Chinese descent. We show that two of the probands of Dutch and Chinese origin have a previously described Arg243His mutation while the patients of German and French descent have a novel Arg243 Cys substitution in their LPL gene. Haplotype analysis is in favour of two separate origins for the Arg243 Cys substitution which together with the Arg243 His mutation would implicate three recurrent mutations involving the first and second nuclcotides of the codon encoding Arg243 of the LPL gene. The recurrent mutations affecting the first and second nucleotide of CGC coding for the normal Arg residue are support for the high mutability of CpG dinucleotides within the LPL gene. © 1994 Wiley-Liss, Inc.

Objectives This study aims to investigate whether family and, the way that children are raised, constitute an influencing factor in the demonstration of intimidating behaviors among children at school environment. Methods Study population consists of 460 students, (2nd and 3rd junior high classes and, 1st class of high school) with a mean of age 14.5 years, who attend in the public secondary educational institutes of the urban area of Heraklion, at Crete, Greece. The measurement instruments used are the Revised Olweus Bully/Victim Questionnaire and, thirteen further questions referring to family, from the general questionnaire of the Health Behavior in School Children research program (launched by WHO). Findings A percentage of 17.5% of the students of the sample were victimized and a 16.5% have participated in bullying others. Furthermore, the majority of students, (40%) in the sample, assess teachers’ counteraction to bullying as “little or nothing” while, only the 2.61% of students feel it as “very”. Students’ involvement in bullying incidents increases when there is no punishment, despite the child's misbehave, or when parents enforce the discipline methods without justification. Moreover, bullying is related with parents’ reluctance to provide assistance on issues towards school. Finally, some parenting behaviors which reflect children's upbringing are connected with bullying. Conclusions The outcomes of this study reveal a significant connection between the bullying behaviors of students and specific parenting behaviors related to the upbringing and discipline methods.

‘Calcium signalling’ is the ubiquitous response of glial cells to multiple extracellular stimuli. The primary mechanism of glial calcium signalling is by release of calcium from intracellular stores of the endoplasmic reticulum (ER). Replenishment of ER Ca2+ stores relies on store-operated calcium entry (SOCE). However, despite the importance of calcium signalling in glial cells, little is known about their mechanisms of SOCE. Here, we investigated SOCE in glia of the mouse optic nerve, a typical CNS white matter tract that comprises bundles of myelinated axons and the oligodendrocytes and astrocytes that support them. Using quantitative RT-PCR, we identified Orai1 channels, both Stim1 and Stim2, and the transient receptor potential M3 channel (TRPM3) as the primary channels for SOCE in the optic nerve, and their expression in both astrocytes and oligodendrocytes was demonstrated by immunolabelling of optic nerve sections and cultures. The functional importance of SOCE was demonstrated by fluo-4 calcium imaging on isolated intact optic nerves and optic nerve cultures. Removal of extracellular calcium ([Ca2+]o) resulted in a marked depletion of glial cytosolic calcium ([Ca2+]i), which recovered rapidly on restoration of [Ca2+]o via SOCE. 2-aminoethoxydiphenylborane (2APB) significantly decreased SOCE and severely attenuated ATP-mediated calcium signalling. The results provide evidence that Orai/Stim and TRPM3 are important components of the ‘calcium toolkit’ that underpins SOCE and the sustainability of calcium signalling in white matter glia.

Glioblastoma Multiforme is a highly aggressive brain tumour known for its heterogeneity and its vascularity. Published reports using in vivo and in vitro glioma models reveal that Matrix metalloproteinase-1 (MMP-1) over-expression induces angiogenesis. In other studies the involvement of the Protease Activated Receptor 1 (PAR1) in MMP-1's effect on tumour vessel formation has been suggested. MMP-1 expression is localised to glioma and endothelial cells with PAR1 expression mainly localised to endothelial cells in human glioma biopsies. MMP-3, also expressed in gliomas, is an activator of pro-MMP-1. Herein, we focused on the effects of MMP-3 activated MMP-1 and conditioned media from glioma cell lines cultured under hypoxic conditions to begin to examine mechanisms of MMP-1 induction of angiogenesis in an in vitro model of brain endothelial cell tube formation. Human brain endothelial cells, activated MMP-1, inhibitors (PAR1 and MMP-1) were used to investigate the possibility that MMP-1 acts through PAR1 to induce angiogenesis. This was accessed by measuring brain endothelial tube length, number of tube projections and the number of branch points. Conditioned media from glioma cell lines (SNB-19 and UP-007) cultured under either normoxic or hypoxic conditions were also tested in the absence/presence of inhibitors. PAR1 activation was examined by endothelial intracellular calcium release using live cell imaging following addition of MMP-1. Exogenous addition of MMP-3 activated MMP-1 to brain endothelial cells lead to a dose dependant increase in number of branch points and tube length (P ≤ 0.05). MMP-1 inhibition prevented this increase and inclusion of a PAR1 inhibitor resulted in preventing MMP-1's effect, suggesting MMP-1 may function through PAR1 to drive angiogenesis. Endothelial cells treated with conditioned media obtained from glioma cell lines resulted in a significant increase in all measures of tube formation, with the most significant effect being on tube number using media from glioma cells grown under hypoxia (P ≤ 0.05). MMP-1 and PAR1 inhibition blocked these effects. Although it is well documented that MMP-1 is over-expressed in high grade gliomas, it has been unclear what role MMP-1 plays as its ‘normal’ ECM substrates are not typically found in gliomas or normal brain. Results from this study extend earlier data showing in vivo induction of angiogenesis and highlight a potential signaling pathway via PAR1 activation in glioma pathology.