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Journal of Neuroendocrinology Mar 2019To understand the contribution of intrinsic membrane properties to the different in vivo firing patterns of oxytocin (OT) and vasopressin (VP) neurones, in vitro studies... (Review)
Review
To understand the contribution of intrinsic membrane properties to the different in vivo firing patterns of oxytocin (OT) and vasopressin (VP) neurones, in vitro studies are needed, where stable intracellular recordings can be made. Combining immunochemistry for OT and VP and intracellular dye injections allows characterisation of identified OT and VP neurones, and several differences between the two cell types have emerged. These include a greater transient K current that delays spiking to stimulus onset, and a higher Na current density leading to greater spike amplitude and a more stable spike threshold, in VP neurones. VP neurones also show a greater incidence of both fast and slow Ca -dependent depolarising afterpotentials, the latter of which summate to plateau potentials and contribute to phasic bursting. By contrast, OT neurones exhibit a sustained outwardly rectifying potential (SOR), as well as a consequent depolarising rebound potential, not found in VP neurones. The SOR makes OT neurones more susceptible to spontaneous inhibitory synaptic inputs and correlates with a longer period of spike frequency adaptation in these neurones. Although both types exhibit prominent Ca -dependent afterhyperpolarising potentials (AHPs) that limit firing rate and contribute to bursting patterns, Ca -dependent AHPs in OT neurones selectively show significant increases during pregnancy and lactation. In OT neurones, but not VP neurones, AHPs are highly dependent on the constitutive presence of the second messenger, phosphatidylinositol 4,5-bisphosphate, which permissively gates N-type channels that contribute the Ca during spike trains that activates the AHP. By contrast to the intrinsic properties supporting phasic bursting in VP neurones, the synchronous bursting of OT neurones has only been demonstrated in vitro in cultured hypothalamic explants and is completely dependent on synaptic transmission. Additional differences in Ca channel expression between the two neurosecretory terminal types suggests these channels are also critical players in the differential release of OT and VP during repetitive spiking, in addition to their importance to the potentials controlling firing patterns.
Topics: Action Potentials; Animals; Humans; Hypothalamus; Membrane Potentials; Neurons; Oxytocin; Vasopressins
PubMed: 30521104
DOI: 10.1111/jne.12666 -
Injury Epidemiology Jan 2021Due to the differences in the way gun law permissiveness scales were created and speculation about the politically motivated underpinnings of the various scales, there...
BACKGROUND
Due to the differences in the way gun law permissiveness scales were created and speculation about the politically motivated underpinnings of the various scales, there have been questions about their reliability.
METHODS
We compared seven gun law permissiveness scales, varying by type and sources, for an enhanced understanding of the extent to which choice of a gun law permissiveness scale could affect studies related to gun violence outcomes in the United States. Specifically, we evaluated seven different scales: two rankings, two counts, and three scores, arising from a range of sources. We calculated Spearman correlation coefficients for each pair of scales compared. Cronbach's standardized alpha and Guttman's lambda were calculated to evaluate the relative reliability of the scales, and we re-calculated Cronbach's alpha after systematically omitting each scale to assess whether the omitted scale contributed to lower internal consistency between scales. Factor analysis was used to determine single factor loadings and estimates. We also assessed associations between permissiveness of gun laws and total firearm deaths and suicides in multivariable regression analyses.
RESULTS
All pairs of scales were highly correlated (average Spearman's correlation coefficient r = 0.77) and had high relative reliability (Cronbach's alpha = 0.968, Guttman's lambda = 0.975). All scales load onto a single factor. The choice of scale did not meaningfully change the parameter estimates for the associations between permissiveness of gun laws and gun deaths and suicides.
CONCLUSION
Gun law permissiveness scales are highly correlated despite any perceived political agenda, and the choice of gun law permissiveness scale has little effect on study conclusions related to gun violence outcomes.
PubMed: 33455576
DOI: 10.1186/s40621-020-00296-5 -
Current Opinion in Pharmacology Oct 2015Adeno-associated viral (AAV) vectors are the most widely used delivery system for in vivo gene therapy. Vectors developed from natural AAV isolates achieved clinical... (Review)
Review
Adeno-associated viral (AAV) vectors are the most widely used delivery system for in vivo gene therapy. Vectors developed from natural AAV isolates achieved clinical benefit for a number of patients suffering from monogenetic disorders. However, high vector doses were required and the presence of pre-existing neutralizing antibodies precluded a number of patients from participation. Further challenges are related to AAV's tropism that lacks cell type selectivity resulting in off-target transduction. Conversely, specific cell types representing important targets for gene therapy like stem cells or endothelial cells show low permissiveness. To overcome these limitations, elegant rational design- as well as directed evolution-based strategies were developed to optimize various steps of AAV's host interaction. These efforts resulted in next generation vectors with enhanced capabilities, that is increased efficiency of cell transduction, targeted transduction of previously non-permissive cell types, escape from antibody neutralization and off-target free in vivo delivery of vector genomes. These important achievements are expected to improve current and pave the way towards novel AAV-based applications in gene therapy and regenerative medicine.
Topics: Animals; Capsid; Cell Nucleus; Dependovirus; Genetic Therapy; Genetic Vectors; Host-Pathogen Interactions; Humans
PubMed: 26302254
DOI: 10.1016/j.coph.2015.08.002 -
Addiction (Abingdon, England) May 2017To estimate whether parental socio-economic status (SES) is associated with adolescent drinking, and the degree to which a possible association may be accounted for by...
AIMS
To estimate whether parental socio-economic status (SES) is associated with adolescent drinking, and the degree to which a possible association may be accounted for by various parental factors.
DESIGN AND SETTING
Cross-sectional Norwegian school survey from 2006 (response rate: 86%).
PARTICIPANTS
Students aged 13-14 years (n = 5797), 15-16 years (n = 6613) and 17-18 years (n = 5351), of whom 51% were girls.
MEASUREMENTS
Parents' education was our main SES indicator, and we distinguished between low (7%) and middle/high (93%) educational level. The outcomes comprised past-year drinking and intoxication. We also applied measures on general parenting, parents' alcohol-related permissiveness and parental intoxication. The main analyses were conducted using Poisson regression.
FINDINGS
Parents' education had no statistically significant impact on alcohol use among the 17-18-year-olds, while 13-16-year-olds with low educated parents had an elevated relative risk (RR) of both drinking [RR = 1.21, 95% confidence interval (CI) = 1.13-1.29] and intoxication (RR = 1.32, 95% CI = 1.21-1.44). The RRs became statistically insignificant when including all the parental factors as covariates in the regression models. Among adolescents who had consumed alcohol, low parental education was related to more frequent drinking (RR = 1.24, 95% CI = 1.11-1.38) and intoxication episodes (RR = 1.42, 95% CI = 1.22-1.66). Again, the RRs became statistically insignificant when we accounted for all the parental factors. This pattern was replicated when we applied an alternative indicator for low parental SES.
CONCLUSIONS
Adolescent drinking in Norway appears to be related inversely to parents' social standing. The elevated risk of low socio-economic status vanishes when general parenting, alcohol-related parental permissiveness and parents' drinking are accounted for.
Topics: Adolescent; Alcoholic Intoxication; Cross-Sectional Studies; Educational Status; Female; Humans; Male; Norway; Parenting; Regression Analysis; Risk; Social Class; Surveys and Questionnaires; Underage Drinking
PubMed: 27943493
DOI: 10.1111/add.13721 -
Gut Microbes 2023Non-caloric artificial sweeteners have been widely permitted as table sugar substitutes with high intensities of sweetness. They can pass through the intestinal tract...
Non-caloric artificial sweeteners have been widely permitted as table sugar substitutes with high intensities of sweetness. They can pass through the intestinal tract without significant metabolization and frequently encounter the gut microbiome, which is composed of diverse bacterial species and is a pool of antibiotic resistance genes (ARGs). However, little is known about whether these sweeteners could accelerate the spread of ARGs in the gut microbiome. Here, we established an conjugation model by using that carries chromosome-inserted Tn7 and plasmid-encoded gene as the donor and murine fecal bacteria as the recipient. We found that four commonly used artificial sweeteners (saccharin, sucralose, aspartame, and acesulfame potassium) can increase reactive oxygen species (ROS) production and promote plasmid-mediated conjugative transfer to the gut microbiome. Cell sorting and 16S rRNA gene amplicon sequencing analysis of fecal samples reveal that the tested sweeteners can promote the broad-host-range plasmid permissiveness to both Gram-negative and Gram-positive gut bacteria. The increased plasmid permissiveness was also validated with a human pathogen . Collectively, our study demonstrates that non-caloric artificial sweeteners can induce oxidative stress and boost the plasmid-mediated conjugative transfer of ARGs among the gut microbiota and a human pathogen. Considering the soaring consumption of these sweeteners and the abundance of mobile ARGs in the human gut, our results highlight the necessity of performing a thorough risk assessment of antibiotic resistance associated with the usage of artificial sweeteners as food additives.
Topics: Mice; Humans; Animals; Gastrointestinal Microbiome; Sweetening Agents; RNA, Ribosomal, 16S; Plasmids; Bacteria; Escherichia coli; Anti-Bacterial Agents; Drug Resistance, Multiple
PubMed: 36524841
DOI: 10.1080/19490976.2022.2157698 -
Heliyon Jul 2023This study compared the experiences of parental abusiveness in childhood and sexual permissiveness in adolescence between adolescents raised by dual parents and those...
OBJECTIVE
This study compared the experiences of parental abusiveness in childhood and sexual permissiveness in adolescence between adolescents raised by dual parents and those raised by single parents.
METHOD
The sampling process involved obtaining the sample size (N = 1037) based on statistical power calculations and the resources available, resulting in representativeness. The sampling frame consisted of students from different backgrounds (single-parent and two-parent families). A stratified random sampling helped to enhance the reliability and validity of the findings while minimizing potential biases. An online survey was used to collect data from the sampled students. An independent sample -test analysis was done by using SPSS software and PROCESS macro of the SPSS to test the hypotheses.
RESULTS
A significant and positive correlation was found between parental abusiveness and sexual permissiveness. There was also a significant mean difference in parental abusiveness experience and sexual permissiveness between adolescents from different family types. In addition, the average sexual permissiveness for males was higher than that of female adolescents from the same type of families.
CONCLUSION
Childhood life significantly influences adolescents' characters throughout their entire life.
PubMed: 37519719
DOI: 10.1016/j.heliyon.2023.e18101 -
Substance Abuse 2022Alcohol is the most used substance among adolescents in Nigeria. While risk factors for alcohol use among adolescents are well documented in Europe and the US, they...
Alcohol is the most used substance among adolescents in Nigeria. While risk factors for alcohol use among adolescents are well documented in Europe and the US, they have received less attention in the literature on African countries. This study aimed to investigate the factors associated with alcohol experimentation and drunkenness episodes in a national sample of Nigerian adolescents. A total sample of 4,078 secondary-school students participated in the survey during the school year 2015-2016. The survey involved 32 secondary schools of six geopolitical zones (South-South, South-West, South-East, North-Center, North-West, and North-East) and two metropolitan cities (Abuja and Lagos) of Nigeria. Sociodemographic characteristics, parental alcohol use and permissiveness, friends' alcohol use, risk perceptions and beliefs were investigated as correlates of alcohol experimentation and drunkenness episodes through multilevel, mixed-effect logistic regression models. The prevalence of alcohol experimentation was 34.0%, while the prevalence of drunkenness episodes was 13.4%. Results showed that male gender, family structure different from both parents' families, parental and friends' alcohol use, parental permissiveness to drink, low risk perceptions on drinking alcohol, and positive beliefs on consequences of alcohol use were associated with an increased probability of alcohol experimentation and drunkenness episodes. Family affluence and one-parent family structure were related to an increased probability of alcohol experimentation but not of drunkenness episodes. The majority of risk factors analyzed in this study generalize across drinking-behavior outcomes. Since the young population is dominant in Nigeria, alcohol use could become a big public health problem in the near future. High investment in adolescents' well-being by addressing the factors that contribute to drinking behavior might help to reduce the burden of the problem. Evidence-based prevention curriculum addressing knowledge, risk perceptions, beliefs on consequences of alcohol use, and parental behaviors should be implemented as widely and early as possible.
Topics: Adolescent; Adolescent Behavior; Alcohol Drinking; Alcoholic Intoxication; Humans; Male; Nigeria; Students
PubMed: 34214414
DOI: 10.1080/08897077.2021.1944952 -
Oncotarget Feb 2019
PubMed: 30899421
DOI: 10.18632/oncotarget.26679 -
Anaesthesia Dec 2017
Topics: Fluid Therapy; Hemorrhage; Humans; Hypotension; Wounds and Injuries
PubMed: 28940420
DOI: 10.1111/anae.14034 -
Journal of the American Academy of... Jul 2019Increasingly permissive attitudes and laws surrounding cannabis have been accompanied by more prevalent use and increased perceptions of its safety. However, in stark...
Increasingly permissive attitudes and laws surrounding cannabis have been accompanied by more prevalent use and increased perceptions of its safety. However, in stark contrast to this sea-change, remarkably little is known about the potential consequences and etiology of cannabis involvement. In particular, it is unclear what biological mechanisms may undergird associations with negative outcomes (eg, reduced cognition, increased psychosis, depression) and whether these substrates arise from cannabis use and/or represent predispositional risk factors. As cannabis remains at the forefront of public discussion and policy, it is increasingly important to identify potential biological mechanisms contributing to associations with negative outcomes and evaluate the plausibility that these represent a consequence of exposure and/or predispositional risk factors or nonetiologic correlates. The knowledge generated from this Herculean task may dam the present sea-change of increasing cannabis permissiveness and/or remove the few remaining boulders impeding it.
Topics: Adolescent; Brain; Cannabis; Cognition; Humans; Marijuana Abuse; Psychotic Disorders
PubMed: 31150755
DOI: 10.1016/j.jaac.2019.05.018