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Evidence has been accumulating regarding alterations in components of the endocannabinoid system in patients with psychosis. Of all the putative risk factors associated with psychosis, being at clinical high-risk for psychosis (CHR) has the strongest association with the onset of psychosis, and exposure to childhood trauma has been linked to an increased risk of development of psychotic disorder. We aimed to investigate whether being at-risk for psychosis and exposure to childhood trauma were associated with altered endocannabinoid levels.
We compared 33 CHR participants with 58 healthy controls (HC) and collected information about previous exposure to childhood trauma as well as plasma samples to analyse endocannabinoid levels.
Individuals with both CHR and experience of childhood trauma had higher N-palmitoylethanolamine (p < 0.001) and anandamide (p < 0.001) levels in peripheral blood compared to HC and those with no childhood trauma. There was also a significant correlation between N-palmitoylethanolamine levels and symptoms as well as childhood trauma.
Our results suggest an association between CHR and/or childhood maltreatment and elevated endocannabinoid levels in peripheral blood, with a greater alteration in those with both CHR status and history of childhood maltreatment compared to those with either of those risks alone. Furthermore, endocannabinoid levels increased linearly with the number of risk factors and elevated endocannabinoid levels correlated with the severity of CHR symptoms and extent of childhood maltreatment. Further studies in larger cohorts, employing longitudinal designs are needed to confirm these findings and delineate the precise role of endocannabinoid alterations in the pathophysiology of psychosis.
The present work aims to explore the mechanism of action of C-cinnamoyl glycoside as an antifilarial agent against the bovine filarial nematode Setaria cervi. Both apoptosis and autophagy programmed cell death pathways play a significant role in parasitic death. The generation of reactive oxygen species, alteration of the level of antioxidant components and disruption of mitochondrial membrane potential may be the causative factors that drive the parasitic death. Monitoring of autophagic flux via the formation of autophagosome and autophagolysosome was detected via CYTO ID dye. The expression profiling of both apoptotic and autophagic marker proteins strongly support the initial findings of these two cell death processes. The increased interaction of pro-autophagic protein Beclin1 with BCL-2 may promote apoptotic pathway by suppressing anti-apoptotic protein BCL-2 from its function. This in turn partially restrains the autophagic pathway by engaging Beclin1 in the complex. But overall positive increment in autophagic flux was observed. Dynamic interaction and regulative balance of these two critical cellular pathways play a decisive role in controlling disease pathogenesis. Therefore, the present experimental work may prosper the chance for C-cinnamoyl glycosides to become a potential antifilarial therapeutic in the upcoming day after detail in vivo study and proper clinical trial.
Evidence regarding the association between cannabis use and depression remain conflicting, especially as studies have not typically adopted a longitudinal design with a follow-up period that was long enough to adequately cover the risk period for onset of depression.
Males from the Cambridge Study in Delinquent Development (CSDD) (N = 285) were assessed seven times from age 8 to 48 years to prospectively investigate the association between cannabis use and risk of major depressive disorder (MDD). A combination of multiple analyses (logistic regression, Cox regression, fixed-effects analysis) was employed to explore the strength and direction of effect within different developmental stages.
Multiple regression analyses revealed that early-onset cannabis use (before age 18) but not late-onset cannabis use (after age 27) was associated with a higher risk and shorter time until a subsequent MDD diagnosis. This effect was present in high-frequency [(odds ratio (OR) 8.83, 95% confidence interval (CI) 1.29–70.79]; [hazard ratio (HR) 8.69, 95% CI 2.07–36.52)] and low-frequency early-onset users (OR 2.41, 95% CI 1.22–4.76; HR 2.09, 95% CI 1.16–3.74). Effect of increased frequency of cannabis use on increased risk of subsequent MDD was observed only for use during adolescence (age 14–18) but not at later life stages, while controlling for observed and non-unobserved time-invariant factors. Conversely, MDD in adulthood (age 18–32) was linked to a reduction in subsequent cannabis use (age 32–48).
The present findings provide evidence implicating frequent cannabis use during adolescence as a risk factor for later life depression. Future studies should further examine causality of effects in larger samples.
Cannabis and its main psychoactive ingredient δ-9-tetrahydrocannibidiol (THC) can induce transient psychotic symptoms in healthy individuals and exacerbate them in those with established psychosis. However, not everyone experience these effects, suggesting that certain individuals are particularly susceptible. The neural basis of this sensitivity to the psychotomimetic effects of THC is unclear.
We investigated whether individuals who are sensitive to the psychotomimetic effects of THC (TP) under experimental conditions would show differential hippocampal activation compared with those who are not (NP). We studied 36 healthy males under identical conditions under the influence of placebo or THC (10 mg) given orally, on two separate occasions, in a pseudo-randomized, double-blind, repeated measures, within-subject, cross-over design, using psychopathological assessments and functional MRI while they performed a verbal learning task. They were classified into those who experienced transient psychotic symptoms (TP; n = 14) following THC administration and those who did not (NP; n = 22).
Under placebo conditions, there was significantly greater engagement of the left hippocampus (p < 0.001) in the TP group compared with the NP group during verbal encoding, which survived leave-one-out analysis. The level of hippocampal activation was directly correlated (Spearman's ρ = 0.44, p = 0.008) with the severity of transient psychotic symptoms induced by THC. This difference was not present when we compared two subgroups from the same sample that were defined by sensitivity to anxiogenic effects of THC.
These results suggest that altered hippocampal activation during verbal encoding may serve as a marker of sensitivity to the acute psychotomimetic effects of THC.
This paper details on the discovery of 21 pulsars using the Giant Metrewave Radio Telescope (GMRT) from targeted (Fermi directed search) and blind surveys (GMRT High Resolution Southern Sky - GHRSS) and results from the follow up studies. We discovered seven millisecond pulsars (MSPs) in the Fermi directed searches, which are the first Galactic MSPs discovered with the GMRT. We have discovered 13 pulsars (including a MSP and two mildly recycled pulsars) with the GHRSS survey, which is an off-Galactic-plane survey at 322 MHz with complementary target sky (declination range −40 deg to −54 deg) to other ongoing low-frequency surveys by GBT and LOFAR. The simultaneous time-domain and imaging study for localising pulsars and transients and efficient candidate investigation with machine learning are some of the features of the GHRSS survey, which are also finding application in the SKA design methodology.
Although the association between cannabis use and violence has been reported in the literature, the precise nature of this relationship, especially the directionality of the association, is unclear.
Young males from the Cambridge Study of Delinquent Development (n = 411) were followed up between the ages of 8 and 56 years to prospectively investigate the association between cannabis use and violence. A multi-wave (eight assessments, T1–T8) follow-up design was employed that allowed temporal sequencing of the variables of interest and the analysis of violent outcome measures obtained from two sources: (i) criminal records (violent conviction); and (ii) self-reports. A combination of analytic approaches allowing inferences as to the directionality of associations was employed, including multivariate logistic regression analysis, fixed-effects analysis and cross-lagged modelling.
Multivariable logistic regression revealed that compared with never-users, continued exposure to cannabis (use at age 18, 32 and 48 years) was associated with a higher risk of subsequent violent behaviour, as indexed by convictions [odds ratio (OR) 7.1, 95% confidence interval (CI) 2.19–23.59] or self-reports (OR 8.9, 95% CI 2.37–46.21). This effect persisted after controlling for other putative risk factors for violence. In predicting violence, fixed-effects analysis and cross-lagged modelling further indicated that this effect could not be explained by other unobserved time-invariant factors. Furthermore, these analyses uncovered a bi-directional relationship between cannabis use and violence.
Together, these results provide strong indication that cannabis use predicts subsequent violent offending, suggesting a possible causal effect, and provide empirical evidence that may have implications for public policy.
In search of a suitable resource conservation technology under pigeonpea (Cajanus cajan L.)–wheat (Triticum aestivum L.) system in the Indo-Gangetic Plains, the effects of conservation agriculture (CA) on crop productivity and water-use efficiency (WUE) were evaluated during a 3-year study. The treatments were: conventional tillage (CT), zero tillage (ZT) with planting on permanent narrow beds (PNB), PNB with residue (PNB + R), ZT with planting on permanent broad beds (PBB) and PBB + R. The PBB + R plots had higher pigeonpea grain yield than the CT plots in all 3 years. However, wheat grain yields under all plots were similar in all years except for PBB + R plots in the second year, which had higher wheat yield than CT plots. The contrast analysis showed that pigeonpea grain yield of CA plots was significantly higher than CT plots in the first year. However, both pigeonpea and wheat grain yields during the last 2 years under CA and CT plots were similar. The PBB + R plots had higher system WUE than the CT plots in the second and third years. Plots under CA had significantly higher WUE and significantly lower water use than CT plots in these years. The PBB + R plots had higher WUE than PNB + R and PNB plots. Also, the PBB plots had higher WUE than PNB in the second and third years, despite similar water use. The interactions of bed width and residue management for all parameters in the second and third years were not significant. Those positive impacts under PBB + R plots over CT plots were perceived to be due to no tillage and significantly higher amount of estimated residue retention. Thus, both PBB and PBB + R technologies would be very useful under a pigeonpea–wheat cropping system in this region.
The aim of this article is to summarize current evidence regarding alterations in the neuroendocrine stress response system and endocannabinoid system and their relationship in psychotic disorders such as schizophrenia. Exposure to stress is linked to the development of a number of psychiatric disorders including psychosis. However, the precise role of stress in the development of psychosis and the possible mechanisms that might underlie this are not well understood. Recently the cannabinoid hypothesis of schizophrenia has emerged as a potential line of enquiry. Endocannabinoid levels are increased in patients with psychosis compared with healthy volunteers; furthermore, they increase in response to stress, which suggests another potential mechanism for how stress might be a causal factor in the development of psychosis. However, research regarding the links between stress and the endocannabinoid system is in its infancy. Evidence summarized here points to an alteration in the baseline tone and reactivity of the hypothalamic–pituitary–adrenal (HPA) axis as well as in various components of the endocannabinoid system in patients with psychosis. Moreover, the precise nature of the inter-relationship between these two systems is unclear in man, especially their biological relevance in the context of psychosis. Future studies need to simultaneously investigate HPA axis and endocannabinoid alterations both at baseline and following experimental perturbation in healthy individuals and those with psychosis to understand how they interact with each other in health and disease and obtain mechanistic insight as to their relevance to the pathophysiology of schizophrenia.
Large areas of rainfed lowlands of Asia annually experienced flash flooding during the rice-growing season, which is an important abiotic stress that adversely affect grain yield of rice (Oryza sativa L.) crop. Submergence stress is a common environmental challenge for agriculture sustainability in these areas because lack of high-yielding, flood-tolerant cultivars. In this study, IR64-Sub1 and IR64 were compared for their tolerance to submergence at active tillering (AT), panicle initiation (PI) and heading (H) stages with nitrogen and phosphorus application time. We evaluated the role of cultivars, stage of submergence and N and P application on phenology, leaf senescence (LS), photosynthetic (Pn) rate, yield attributes and yield. Under non-submerged conditions, no difference was observed in phenology, Pn rate and yield of both cultivars. Submergence substantially reduced biomass, Pn rate, yields attributes and yield across cultivars with more drastic reduction in IR64. Submergence at H stage proves to be most detrimental. Nitrogen application after desubmergence with basal P improved the Pn rate resulting in significantly higher yield and yield components. Nitrogen application before submergence resulted in increased LS and ethylene accumulation in shoots leading to drastic reduction in growth, Pn rate and yield. Crop establishment and productivity could therefore be enhanced in areas where untimely flooding is anticipated by avoiding N application before submergence and applying N after desubmergence with basal P (phosphorus).
A suite of sheared syenites occurring along the western margin of the Eastern Ghats Belt, India have developed extensive flame perthite in K-feldspar. Albite flames show large variation in size, shape and abundance. Field, petrographic and chemical evidence suggests complex interplay between differential stress, recycling of K-Na-Ca and supply of Na by infiltration for the development of flame perthite. Partial replacement of pyroxenes, plagioclase and alkali feldspar by amphibole, biotite, nepheline and calcite causes internal recycling of Na-Ca-K in a closed system. Representative compositions of the minerals are used to constrain the model dissolution–reprecipitation ion-exchange reactions involving Na and K either as reactants and/or as products. A substantial proportion of Na+ required for the development of the albite flames, originates from Na metasomatism accompanied by ductile shearing in the feldspathic rocks, providing an ideal open system wherein both the differential stress and Na+ are made available for the development of the flame perthites. This process probably augmented the replacement of K-feldspar grains by flame albite and the K+ released was carried away by the fluid or, possibly, augmented the biotite-forming reactions in the associated quartz-poor syenites and, hence, trigger the Na-K cycle in these rocks.
This paper reports a study of local orientation change occurring within micro-scale tensile samples as a function of strain. These samples were fabricated from a thin film of single crystal bcc Fe and deformed in tension using an in situ micro-mechanical testing device inside a scanning electron microscope. Samples were loaded along the <110> direction parallel to the specimen axis, strained to different levels, and then subjected to electron backscatter diffraction scans over the entire area of the gauge section. Analysis of the surface orientation data shows that, within a necked zone of the micro-sample gauge section, there are two distinct regions of significant orientation change, in which local crystal rotations occur in opposite directions. These two regions are separated by an intermediate band that shows minimal misorientation from the original state. Crystal rotations within the two regions that develop opposite orientations are found to be consistent with classic single crystal slip, where the slip direction rotates toward the tensile axis. It is shown that increasing tensile strain causes an increasing degree of rotation away from the starting orientation. The tests also illustrate the occurrence of slip on at least two different slip systems, based on the slip traces and orientation change.
Scanning electron microscopy (SEM) of scales in six species of the fish genus Channa revealed certain features relevant to taxonomic significance. The location of focus, inter-radial distance and width of circuli, inter-circular space, width of radii, shape and size of lepidonts, etc. were found to be different in different species. The importance of SEM of scales in poorly understood taxonomy and phylogeny of the fish genus Channa is discussed with the help of relevant literature. Further, the role of SEM of fish scales for taxonomic applications is discussed in detail.
What determines inter-individual variability to impairments in behavioural control that may underlie road-traffic accidents, and impulsive and violent behaviours occurring under the influence of cannabis, the most widely used illicit drug worldwide?
Employing a double-blind, repeated-measures design, we investigated the genetic and neural basis of variable sensitivity to cannabis-induced behavioural dyscontrol in healthy occasional cannabis users. Acute oral challenge with placebo or Δ9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, was combined with functional magnetic resonance imaging, while participants performed a response inhibition task that involved inhibiting a pre-potent motor response. They were genotyped for rs1130233 single nucleotide polymorphisms (SNPs) of the protein kinase B (AKT1) gene.
Errors of inhibition were significantly (p = 0.008) increased following administration of THC in carriers of the A allele, but not in G allele homozygotes of the AKT1 rs1130233 SNP. The A allele carriers also displayed attenuation of left inferior frontal response with THC evident in the sample as a whole, while there was a modest enhancement of inferior frontal activation in the G homozygotes. There was a direct relationship (r = − 0.327, p = 0.045) between the behavioural effect of THC and its physiological effect in the inferior frontal gyrus, where AKT1 genotype modulated the effect of THC.
These results require independent replication and show that differing vulnerability to acute psychomotor impairments induced by cannabis depends on variation in a gene that influences dopamine function, and is mediated through modulation of the effect of cannabis on the inferior frontal cortex, that is rich in dopaminergic innervation and critical for psychomotor control.
Cannabis use is associated with an increased risk of developing a psychotic disorder but the temporal relationship between cannabis use and onset of illness is unclear. The objective of this study was to assess prospectively the influence of cannabis use on transition to psychosis in people at ultra-high risk (UHR) for the disorder.
Lifetime and continued cannabis use was assessed in a consecutively ascertained sample of 182 people (104 male, 78 female) at UHR for psychosis. Individuals were then followed clinically for 2 years to determine their clinical outcomes.
Lifetime cannabis use was reported by 134 individuals (73.6%). However, most of these individuals had stopped using cannabis before clinical presentation (n = 98, 73.1%), usually because of adverse effects. Among lifetime users, frequent use, early-onset use and continued use after presentation were all associated with an increase in transition to psychosis. Transition to psychosis was highest among those who started using cannabis before the age of 15 years and went on to use frequently (frequent early-onset use: 25%; infrequent or late-onset use: 5%; χ21 = 10.971, p = 0.001). However, within the whole sample, cannabis users were no more likely to develop psychosis than those who had never used cannabis (cannabis use: 12.7%; no use: 18.8%; χ21 = 1.061, p = 0.303).
In people at UHR for psychosis, lifetime cannabis use was common but not related to outcome. Among cannabis users, frequent use, early-onset use and continued use after clinical presentation were associated with transition to psychosis.
Drug-resistant Mycobacterium tuberculosis bacterium (MTB) is spreading worldwide. Three drug-resistant isolates were detected in Burmese, Hmong, and Indian immigrants currently residing in Milwaukee, Wisconsin, USA. Ion Torrent full-gene sequencing and complete genetic analysis was performed within 5 days and compared to results from traditional drug sensitivity testing (DST). Genetic characterization of seven, full-length resistance-associated genes revealed two MDR and one highly resistant strain with important drug-resistant mutations that were confirmed by traditional DST. The rapid turnaround from sample-to-sequence underscores the public health value of Ion Torrent full-gene sequencing of MDR/XDR genes from epidemiologically significant clinical isolates.
Cannabis can induce transient psychotic symptoms, but not all users experience these adverse effects. We compared the neural response to Δ9-tetrahydrocannabinol (THC) in healthy volunteers in whom the drug did or did not induce acute psychotic symptoms.
In a double-blind, placebo-controlled, pseudorandomized design, 21 healthy men with minimal experience of cannabis were given either 10 mg THC or placebo, orally. Behavioural and functional magnetic resonance imaging measures were then recorded whilst they performed a go/no-go task.
The sample was subdivided on the basis of the Positive and Negative Syndrome Scale positive score following administration of THC into transiently psychotic (TP; n = 11) and non-psychotic (NP; n = 10) groups. During the THC condition, TP subjects made more frequent inhibition errors than the NP group and showed differential activation relative to the NP group in the left parahippocampal gyrus, the left and right middle temporal gyri and in the right cerebellum. In these regions, THC had opposite effects on activation relative to placebo in the two groups. The TP group also showed less activation than the NP group in the right middle temporal gyrus and cerebellum, independent of the effects of THC.
In this first demonstration of inter-subject variability in sensitivity to the psychotogenic effects of THC, we found that the presence of acute psychotic symptoms was associated with a differential effect of THC on activation in the ventral and medial temporal cortex and cerebellum, suggesting that these regions mediate the effects of the drug on psychotic symptoms.
Interpersonal sensitivity is a personality trait described as excessive awareness of both the behaviour and feelings of others. Although interpersonal sensitivity has been found to be one of the vulnerability factors to depression, there has been little interest in its relationship with the prodromal phase of psychosis. The aims of this study were to examine the level of interpersonal sensitivity in a sample of individuals with an at-risk mental state (ARMS) for psychosis and its relationship with other psychopathological features.
Method. Sixty-two individuals with an ARMS for psychosis and 39 control participants completed a series of self-report questionnaires, including the Interpersonal Sensitivity Measure (IPSM), the Prodromal Questionnaire (PQ), the Ways of Coping Questionnaire (WCQ) and the Depression and Anxiety Stress Scale (DASS).
Individuals with an ARMS reported higher interpersonal sensitivity compared to controls. Associations between interpersonal sensitivity, positive psychotic symptoms (i.e. paranoid ideation), avoidant coping and symptoms of depression, anxiety and stress were also found.
This study suggests that being ‘hypersensitive’ to interpersonal interactions is a psychological feature of the putatively prodromal phase of psychosis. The relationship between interpersonal sensitivity, attenuated positive psychotic symptoms, avoidant coping and negative emotional states may contribute to long-term deficits in social functioning. We illustrate the importance, when assessing a young client with a possible ARMS, of examining more subtle and subjective symptoms in addition to attenuated positive symptoms.
We conducted a systematic review to assess the evidence for specific effects of cannabis on brain structure and function. The review focuses on the cognitive changes associated with acute and chronic use of the drug.
We reviewed literature reporting neuroimaging studies of chronic or acute cannabis use published up until January 2009. The search was conducted using Medline, EMBASE, LILACS and PsycLIT indexing services using the following key words: cannabis, marijuana, delta-9-tetrahydrocannabinol, THC, cannabidiol, CBD, neuroimaging, brain imaging, computerized tomography, CT, magnetic resonance, MRI, single photon emission tomography, SPECT, functional magnetic resonance, fMRI, positron emission tomography, PET, diffusion tensor MRI, DTI-MRI, MRS and spectroscopy.
Sixty-six studies were identified, of which 41 met the inclusion criteria. Thirty-three were functional (SPECT/PET/fMRI) and eight structural (volumetric/DTI) imaging studies. The high degree of heterogeneity across studies precluded a meta-analysis. The functional studies suggest that resting global and prefrontal blood flow are lower in cannabis users than in controls. The results from the activation studies using a cognitive task are inconsistent because of the heterogeneity of the methods used. Studies of acute administration of THC or marijuana report increased resting activity and activation of the frontal and anterior cingulate cortex during cognitive tasks. Only three of the structural imaging studies found differences between users and controls.
Functional neuroimaging studies suggest a modulation of global and prefrontal metabolism both during the resting state and after the administration of THC/marijuana cigarettes. Minimal evidence of major effects of cannabis on brain structure has been reported.
Nanoscale metallic multilayers, comprising two sets of materials—Cu/Nb and Cu/Ni—were deposited in two different layer thicknesses—nominally 20 and 5 nm. These multilayer samples were indented, and the microstructural changes under the indent tips were studied by extracting samples from underneath the indents using the focused ion beam (FIB) technique and by examining them under a transmission electron microscope (TEM). The deformation behavior underneath the indents, manifested in the bending of layers, reduction in layer thickness, shear band formation, dislocation crossing of interfaces, and orientation change of grains, has been characterized and interpreted in terms of the known deformation mechanisms of nanoscale multilayers.