A mouse model for chronic pain-induced increase in ethanol consumption

Chronic pain conditions are often co-morbid with alcohol abuse. “Self-medication” with alcohol introduces a host of problems associated with the abuse of alcohol which over time has the potential of exacerbating the painful condition. Despite the prevalence of chronic pain being associated with alcohol abuse, rodent models which mimic the co-morbid conditions are lacking. In the present study, we model osteoarthritis (OA) in C57BL/6J mice by surgically destabilizing the medial meniscus (DMM). Sham operated mice served as controls. Thirteen weeks after surgery, DMM but not sham operated mice exhibited pronounced incapacitance of the surgically-manipulated hindlimb compared to the non-surgically manipulated hindlimb. At this time, the mice were exposed to the two-bottle ethanol choice, beginning with 2.5% with a gradual increasing to 20%. Compared to sham controls, DMM mice consumed more EtOH and preferred EtOH over water at the 20% EtOH concentration. Histological analysis verified that the DMM mice exhibited significant damage to the articular cartilage and osteophyte growth compared to sham controls and these measures of the severity of OA correlated with the amount of ethanol intake. Thus, the combination of the DMM model of OA with the enhanced two-bottle ethanol choice is a potential preclinical approach in mice by which the basis of the co-morbid association of alcohol abuse and chronic pain conditions can be explored

Supervised physical activity and the incidence of gestational diabetes mellitus: a systematic review and meta-analysis

Background: Gestational diabetes mellitus (GDM) characterized by dysfunction in maintaining glucose homeostasis is recognized as the most common metabolic complication associated with pregnancy leading to adverse clinical outcomes for maternal and fetal health. Although previous analysis of the findings from randomized controlled trials (RCTs) support that regular physical activity reduces the incidence of GDM during pregnancy, less is known about the optimal timing of intervention with respect to trimester stage. Objectives: To examine the interaction between both the timing and volume of supervised physical activity interventions on reducing the incidence of GDM during pregnancy. Study design: Electronic databases including CINAHL, Embase, Medline and the Cochrane library were searched for records up to 29 September 2022. Eligibility criteria were RCTs including standard antenatal care þ supervised physical activity intervention without dietary modification vs. those receiving standard antenatal care alone in women with no previous diagnosis of GDM, type 1 or type 2 diabetes mellitus. Results: Of the 3411 records identified, 20 RCTs comprising 6732 participants were included. It was found that supervised physical activity interventions decreased GDM risk when started within the first trimester (RR: 0.57, 95% CI: 0.41–0.79; p ¼ .001) and by accumulating >600 METminwk1 of exercise (RR: 0.77, 95% CI: 0.60–0.98; p ¼ .03) compared with standard antenatal care alone. Women with a BMI 25 kg/m2 experienced the greatest risk reduction in GDM following supervised exercise training (RR: 0.51, 95% CI: 0.34–0.75; p ¼ .001). Conclusion: Supervised physical activity reduces the incidence of GDM during pregnancy. It is recommended that pregnant individuals achieve a minimum of 600 METminwk1 of physical activity during the first trimester in order to reduce their odds of developing GDM. Attaining a healthy pre-pregnancy BMI is also an important determinant for the prevention of GDM with exercise

The improvement of crop yield in marginal environments using ‘on-farm’ seed priming: nodulation, nitrogen fixation, and disease resistance

On-farm seed priming with water is a low-cost, low-risk technology that is easily adopted by resource-poor farmers. It increases the yield of tropical and subtropical annual crops in marginal areas by a combination of better crop establishment and improved individual plant performance. The effects of seed priming, i.e. soaking seeds overnight in water before sowing, on plant growth and development are consequences of faster germination, emergence, and more vigorous early growth. Results from in-vitro, on-station and on-farmexperiments are discussed. Recent work has tested opportunities for resource-poor farmers to use seed priming as a vehicle for applying biofertilisers (Rhizobia). Preliminary results from field experiments suggest that these interventions are very effective over and above the already demonstrated benefits of priming with water alone. In a pot experiment using chickpea, combining a Rhizobium inoculation with seed priming significantly increased nodulation but had little effect on yield. Nevertheless, the results confirmed that Rhizobium inoculation is compatible with on-farm seed priming. Observations in the field have shown that some primed crops show enhanced resistance to disease, either as a consequence of increased vigour, altered phenology, or due to some more fundamental mechanism associated with exposure of seeds to anaerobic conditions during priming. Priming seeds of a highly susceptible cultivar of pearl millet in water for 8 h before sowing significantly reduced the incidence of downy mildew in artificially infected seedlings from 80% to less than 60%

Topographic patterns of brain activity in response to swim stress: assessment by 2-deoxyglucose uptake and expression of Fos-like immunoreactivity

Alterations in brain activity patterns were assessed in response to swim stress by immunocytochemical detection of Fos-like immunoreactivity (Fos-LI) and high-resolution autoradiographic imaging of 14C-2-deoxyglucose (2-DG) uptake. The stress paradigm investigated was a classic behavioral screen for antidepressant drug activity, the forced swim test. One of the most pronounced effects produced by swim stress was an increase in 2-DG uptake and induction of Fos-LI in a restricted region of the lateral septal nucleus. Specific "limbic" cortical regions, including the medial prefrontal, ventrolateral orbital, and cingulate cortices, also exhibited both increased 2-DG uptake and expression of Fos-LI in response to swim stress. In the hypothalamic paraventricular nucleus of swim-stressed rats, Fos-LI was induced but no change in 2-DG uptake was apparent. Since the specific swim stress protocol used is a behavioral screen for antidepressant drugs, the effects of imipramine on stress-induced alterations in 2-DG uptake and induction of Fos-LI were examined. The stress-induced increase in 2-DG uptake in the lateral septum was blocked by treatment with imipramine, but treatment with imipramine had no effect on induction of Fos-LI in the same region. Neither 2-DG uptake nor Fos-LI expression was altered by imipramine treatment in the cortical regions influenced by swim stress. Administration of imipramine alone under basal conditions produced a robust induction of Fos-LI in the central nucleus of the amygdala and in the dorsal lateral subdivision of the bed nucleus of the stria terminalis. No effect of imipramine treatment on 2-DG uptake was apparent in these latter regions. The results provide insights into topographic patterns of brain activity associated with swim stress and neuroanatomically selective actions of imipramine. The different and complementary information obtained by assessment of Fos-LI and 2-DG uptake illustrates the utility of applying both functional mapping approaches to examine neuroanatomical correlates of behavioral states and drug treatment

Hypothalamic neuronal histamine mediates the thyrotropin-releasing hormone-induced suppression of food intake1

We examined the involvement of thyrotropin-releasing hormone (TRH) and TRH type 1 and 2 receptors (TRH-R1 and TRH-R2, respectively) in the regulation of hypothalamic neuronal histamine. Infusion of 100 nmol TRH into the rat third cerebroventricle (3vt) significantly decreased food intake (p < 0.05) compared to controls infused with phosphate- buffered saline. This TRH-induced suppression of food intake was attenuated partially in histamine-depleted rats pre-treated with α-fluoromethylhistidine (a specific suicide inhibitor of histidine decarboxylase) and in mice with targeted disruption of histamine H1 receptors. Infusion of TRH into the 3vt increased histamine turnover as assessed by pargyline-induced accumulation of tele-methylhistamine (t-MH, a major metabolite of neuronal histamine in the brain) in the tuberomammillary nucleus (TMN), the paraventricular nucleus, and the ventromedial hypothalamic nucleus in rats. In addition, TRH-induced decrease of food intake and increase of histamine turnover were in a dose-dependent manner. Microinfusion of TRH into the TMN increased t-MH content, histidine decarboxylase (HDC) activity and expression of HDC mRNA in the TMN. Immunohistochemical analysis revealed that TRH-R2, but not TRH-R1, was expressed within the cell bodies of histaminergic neurons in the TMN of rats. These results indicate that hypothalamic neuronal histamine mediates the TRH-induced suppression of feeding behavior

Cationic vacancy induced room-temperature ferromagnetism in transparent conducting anatase Ti_{1-x}Ta_xO_2 (x~0.05) thin films

We report room-temperature ferromagnetism in highly conducting transparent anatase Ti1-xTaxO2 (x~0.05) thin films grown by pulsed laser deposition on LaAlO3 substrates. Rutherford backscattering spectrometry (RBS), x-ray diffraction (XRD), proton induced x-ray emission (PIXE), x-ray absorption spectroscopy (XAS) and time-of-flight secondary ion mass spectrometry (TOF-SIMS) indicated negligible magnetic contaminants in the films. The presence of ferromagnetism with concomitant large carrier densities was determined by a combination of superconducting quantum interference device (SQUID) magnetometry, electrical transport measurements, soft x-ray magnetic circular dichroism (SXMCD), XAS, and optical magnetic circular dichroism (OMCD) and was supported by first-principle calculations. SXMCD and XAS measurements revealed a 90% contribution to ferromagnetism from the Ti ions and a 10% contribution from the O ions. RBS/channelling measurements show complete Ta substitution in the Ti sites though carrier activation was only 50% at 5% Ta concentration implying compensation by cationic defects. The role of Ti vacancy and Ti3+ was studied via XAS and x-ray photoemission spectroscopy (XPS) respectively. It was found that in films with strong ferromagnetism, the Ti vacancy signal was strong while Ti3+ signal was absent. We propose (in the absence of any obvious exchange mechanisms) that the localised magnetic moments, Ti vacancy sites, are ferromagnetically ordered by itinerant carriers. Cationic-defect-induced magnetism is an alternative route to ferromagnetism in wide-band-gap semiconducting oxides without any magnetic elements.Comment: 21 pages, 10 figures, to appear in Philosophical Transaction - Royal Soc.

Brain Regional Differences in the Effect of Ethanol on GABA Release from Presynaptic Terminals

Whereas ethanol has behavioral actions consistent with increased GABAergic function, attempts to demonstrate a direct enhancement of GABA-gated currents by ethanol have produced mixed results. Recent work has suggested that a part of the GABAergic profile of ethanol may result from enhanced GABA release from presynaptic terminals. The present study examines the effect of ethanol on GABA release in several brain regions to assess the regional nature of ethanol-induced GABA release. Whole-cell voltage clamp recording of spontaneous inhibitory postsynaptic currents (sIPSCs) from mechanically dissociated neurons and miniature inhibitory postsynaptic currents (mIPSCs) and paired-pulse ratio (PPR) from a slice preparation were used to quantify GABA release. Ethanol produced a concentration-dependent increase in the frequency of sIPSCs recorded from mechanically dissociated cerebellar Purkinje neurons and mIPSCs from substantia nigra neurons without having an effect on sIPSCs recorded from lateral septal or cerebrocortical neurons. This regional difference in the effect of ethanol on GABA release was confirmed with PPR recording from brain slices. These data indicate that ethanol can act on presynaptic terminals to increase GABA release in some brain regions while having little or no effect on GABA release in others. This regional difference is consistent with earlier in vivo studies in which ethanol affected neural activity and sensitivity to GABA in some, but not all, brain sites

The effect of layer number and substrate on the stability of graphene under MeV proton beam irradiation

The use of graphene electronics in space will depend on the radiation hardness of graphene. The damage threshold of graphene samples, subjected to 2 MeV proton irradiation, was found to increase with layer number and also when the graphene layer was supported by a substrate. The thermal properties of graphene as a function of the number of layers or as influenced by the substrate argue against a thermal model for the production of damage by the ion beam. We propose a model of intense electronically-stimulated surface desorption of the atoms as the most likely process for this damage mechanism.Comment: 20 pages, 5 figure

Enhanced muscimol-induced behavioral responses after 6-OHDA lesions: relevance to susceptibility for self-mutilation behavior in neonatally lesioned rats

Adult rats lesioned with 6-hydroxydopamine (6-OHDA), either as neonates or as adults, demonstrated increased turning, compared to unlesioned controls, when muscimol was unilaterally microinjected into the substantia nigra reticulata (SNR). At the higher doses of muscimol, the lesioned rats were so intensely lateralized that circling was impeded. These data suggest a functional supersensitivity of receptors associated with GABA function in the SNR of 6-OHDA-lesioned rats. When 30 ng muscimol was administered bilaterally into the SNR, self-mutilation behavior (SMB) was observed in 2/11 of the control unlesioned rats, in 0/8 adult 6-OHDA-lesioned rats, and in 11/11 of the neonatally-lesioned rats tested. The ability of muscimol to produce SMB in the rats lesioned as neonates was dose related. Behavioral observations indicated that behaviors associated with SMB (self-biting and taffy pulling) were present in neonatal, but not adult lesioned rats. Behavioral responses to dopamine agonist administration were also different between rats lesioned as neonates and those lesioned as adults with 6-OHDA. These data support the view that lesions of dopaminergic neurons cause an increased functional responsiveness of receptors acted upon by muscimol in the SNR, and that the increased susceptibility for SMB in neonatally lesioned rats is determined by neurons distal to the GABA receptor complex in the SNR

Channeling of Positrons through Periodically Bent Crystals: on Feasibility of Crystalline Undulator and Gamma-Laser

The electromagnetic radiation generated by ultra-relativistic positrons channelling in a crystalline undulator is discussed. The crystalline undulator is a crystal whose planes are bent periodically with the amplitude much larger than the interplanar spacing. Various conditions and criteria to be fulfilled for the crystalline undulator operation are established. Different methods of the crystal bending are described. We present the results of numeric calculations of spectral distributions of the spontaneous radiation emitted in the crystalline undulator and discuss the possibility to create the stimulated emission in such a system in analogy with the free electron laser. A careful literature survey covering the formulation of all essential ideas in this field is given. Our investigation shows that the proposed mechanism provides an efficient source for high energy photons, which is worth to study experimentally.Comment: 52 pages, MikTeX, 14 figure