RATIONALE:Preclinical studies report that drug use and social contact mutually influence the reinforcing effects of one another. Most of these studies have used same-sex dyads exclusively, and the role of factors related to biological sex and hormonal fluctuations are not well understood. OBJECTIVES:The purpose of this study was to examine the reinforcing effects of cocaine and social contact with an opposite-sex partner in male and female rats, and how these effects are modulated by ovarian hormones. METHODS:Male and female rats were trained in a nonexclusive choice procedure in which cocaine and social contact with an opposite-sex partner were simultaneously available on concurrent progressive ratio schedules of reinforcement. To examine the effects of ovarian hormones related to estrous cycling, Experiment 1 used naturally cycling, gonadally intact females, whereas Experiment 2 used ovariectomized females, and estrus was artificially induced with exogenous hormones. RESULTS:In both experiments, cocaine and social contact functioned as robust reinforcers, and there were no significant effects of biological sex or estrus status of the females. The positive reinforcing effects of both cocaine and social contact increased as a function of cocaine dose, indicating that contingent cocaine administration increases the reinforcing effects of social contact. CONCLUSIONS:These data suggest that cocaine use among opposite-sex partners may enhance factors that contribute to social bonding.
The economically valuable Brassica species include the six related members of U's Triangle. Despite the agronomic and economic importance of these Brassicas, the impacts of evolution and relatively recent domestication events on the genetic landscape of seed development have not been comprehensively examined in these species. Here we present a 3D transcriptome atlas for the six species of U's Triangle, producing a unique resource that captures gene expression data for the major subcompartments of the seed, from the unfertilized ovule to the mature embryo and seed coat. This comprehensive dataset for seed development in tetraploid and ancestral diploid Brassicas provides new insights into evolutionary divergence and expression bias at the gene and subgenome levels during the domestication of these valued crop species. Comparisons of gene expression associated with regulatory networks and metabolic pathways operating in the embryo and seed coat during seed development reveal differences in storage reserve accumulation and fatty acid metabolism among the six Brassica species. This study illustrates the genetic underpinnings of seed traits and the selective pressures placed on seed production, providing an immense resource for continued investigation of Brassica polyploid biology, genomics and evolution.
Heroin intake decreases markedly during proestrus in normally cycling female rats; however, it is not known whether estradiol, progesterone, or both hormones are responsible for these decreases in heroin intake. The purpose of the present study was to examine the roles of estradiol and progesterone in heroin intake by artificially inducing a proestrus state in ovariectomized rats. To this end, ovariectomized female rats were implanted with intravenous catheters and trained to self-administer heroin (0.0075 mg/kg/infusion) on a fixed ratio (FR1) schedule of reinforcement. After 1 week of training, rats were tested at weekly intervals with estradiol (0.005 mg, sc) or vehicle 22 hr before a test session and progesterone (0.125 mg, sc) or vehicle 0.5 hr before a test session to artificially mimic the naturally occurring hormone concentrations characteristic of late proestrus. Administration of estradiol 22 hr prior to testing and progesterone 0.5 hr prior to testing significantly reduced heroin intake relative to the previous training day and vehicle control. It is interesting that this same effect was observed when only estradiol, but not progesterone, was administered. These data suggest that estradiol but not progesterone is responsible for the proestrus-induced decreases in heroin intake previously reported in normally cycling female rats. These findings differ from those reported previously with stimulants and suggest that estrogen-based pharmacotherapies may be of value to women with opioid use disorder. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Heroin intake decreases during the proestrus phase of the estrous cycle in female, Long-Evans rats. The purpose of this study was to (1) determine if proestrus-associated decreases in heroin intake extend across rat strains and (2) determine if proestrus-associated decreases in responding extend to a nondrug reinforcer. Female rats were implanted with intravenous catheters and trained to self-administer heroin. Estrous cycle was tracked daily for the duration of the study. During testing, Lewis, Sprague Dawley, and Long-Evans rats self-administered low (0.0025 mg/kg) and high (0.0075 mg /kg) doses of heroin and then self-administered sugar on fixed ratio (FR1) schedules of reinforcement. Heroin intake decreased significantly during proestrus in all three rat strains under at least one dose condition; however, sugar intake did not decrease during proestrus in any strain. These data suggest that responding maintained by heroin, but not a nondrug reinforcer, significantly decreases during proestrus in female rats and that these effects are consistent across rat strain.
Arcuate nucleus agouti-related peptide (AgRP) neurons play a central role in feeding and are under complex regulation by both homeostatic hormonal and nutrient signals and hypothalamic neuronal pathways. Feeding may also be influenced by environmental cues, sensory inputs, and other behaviors, implying the involvement of higher brain regions. However, whether such pathways modulate feeding through direct synaptic control of AgRP neuron activity is unknown. Here, we show that nociceptin-expressing neurons in the anterior bed nuclei of the stria terminalis (aBNST) make direct GABAergic inputs onto AgRP neurons. We found that activation of these neurons inhibited AgRP neurons and feeding. The activity of these neurons increased upon food availability, and their ablation resulted in obesity. Furthermore, these neurons received afferent inputs from a range of upstream brain regions as well as hypothalamic nuclei. Therefore, aBNST GABAergic nociceptin neurons may act as a gateway to feeding behavior by connecting AgRP neurons to both homeostatic and nonhomeostatic neuronal inputs.
Mechanical stimulation of fibroblasts induces changes in the actin cytoskeleton including stress fiber (SF) reinforcement and realignment. Here we characterize the nuclear response to mechanical stimulation (uniaxial cyclic stretch). Using fluorescence microscopy and quantitative image analysis we find that stretch-induced nuclear elongation and alignment perpendicular to the stretch vector are dependent on formin-regulated actin polymerization. The mechanosensitive transcription factors Yes-associated protein/Transcriptional coactivator with PDZ domain (YAP/TAZ) and myocardin-related transcription factor (MRTF-A, also known as MKL1 and MAL1) accumulate in the nucleus and activate their target genes in response to uniaxial cyclic stretch. We show that transmembrane actin nuclear (TAN) lines are induced by stretch stimulation and nuclear envelope (NE) proteins including nesprins, SUN2, and lamins form Linkers of the Nucleoskeleton and Cytoskeleton (LINC) complexes aligned with actin SFs. These NE structures are altered by pharmacological treatments (Cytochalasin D and Jasplakinolide) or genetic disruption (zyxin gene deletion) that alter actin, and their persistence requires maintenance of stretch stimulation. Nuclear pore complexes (NPCs) accumulate at TAN lines providing a potential mechanism for linking mechanical cues to NPC function.
Production of hydroxy fatty acids (HFAs) in transgenic crops represents a promising strategy to meet our demands for specialized plant oils with industrial applications. The expression of Ricinus communis (castor) OLEATE 12-HYDROXYLASE (RcFAH12) in Arabidopsis has resulted in only limited accumulation of HFAs in seeds, which probably results from inefficient transfer of HFAs from their site of synthesis (phosphatidylcholine; PC) to triacylglycerol (TAG), especially at the sn-1/3 positions of TAG. Phospholipase As (PLAs) may be directly involved in the liberation of HFAs from PC, but the functions of their over-expression in HFA accumulation and distribution at TAG in transgenic plants have not been well studied. In this work, the functions of lecithin:cholesterol acyltransferase-like PLAs (LCAT-PLAs) in HFA biosynthesis were characterized. The LCAT-PLAs were shown to exhibit homology to LCAT and mammalian lysosomal PLA(2), and to contain a conserved and functional Ser/His/Asp catalytic triad. In vitro assays revealed that LCAT-PLAs from the HFA-accumulating plant species Physaria fendleri (PfLCAT-PLA) and castor (RcLCAT-PLA) could cleave acyl chains at both the sn-1 and sn-2 positions of PC, and displayed substrate selectivity towards sn-2-ricinoleoyl-PC over sn-2-oleoyl-PC. Furthermore, co-expression of RcFAH12 with PfLCAT-PLA or RcLCAT-PLA, but not Arabidopsis AtLCAT-PLA, resulted in increased occupation of HFA at the sn-1/3 positions of TAG as well as small but insignificant increases in HFA levels in Arabidopsis seeds compared with RcFAH12 expression alone. Therefore, PfLCAT-PLA and RcLCAT-PLA may contribute to HFA turnover on PC, and represent potential candidates for engineering the production of unusual fatty acids in crops.
Castor patatin-like phospholipase A IIIβ facilitates the exclusion of hydroxy fatty acids from phosphatidylcholine in developing transgenic Arabidopsis seeds. Hydroxy fatty acids (HFAs) are industrial useful, but their major natural source castor contains toxic components. Although expressing a castor OLEATE 12-HYDROXYLASE in Arabidopsis thaliana leads to the synthesis of HFAs in seeds, a high proportion of the HFAs are retained in phosphatidylcholine (PC). Thus, the liberation of HFA from PC seems to be critical for obtaining HFA-enriched seed oils. Plant phospholipase A (PLA) catalyzes the hydrolysis of PC to release fatty acyl chains that can be subsequently channeled into triacylglycerol (TAG) synthesis or other metabolic pathways. To further our knowledge regarding the function of PLAs from HFA-producing plant species, two class III patatin-like PLA cDNAs (pPLAIIIβ or pPLAIIIδ) from castor or Physaria fendleri were overexpressed in a transgenic line of A. thaliana producing C18-HFA, respectively. Only the overexpression of RcpPLAIIIβ resulted in a significant reduction in seed HFA content with concomitant changes in fatty acid composition. Reductions in HFA content occurred in both PC and TAG indicating that HFAs released from PC were not incorporated into TAG. These results suggest that RcpPLAIIIβ may catalyze the removal of HFAs from PC in the developing seeds synthesizing these unusual fatty acids.
Objective: There is limited information to guide health-care service providers and policy makers on the burden of mental disorders and addictions across the Canadian provinces. This study compares interprovincial prevalence of major depressive disorder (MDD), bipolar disorder, generalized anxiety disorder (GAD), alcohol use disorder, substance use disorders, and suicidality. Method: Data were extracted from the 2012 Canadian Community Health Survey—Mental Health (n = 25,113), a representative sample of Canadians over the age of 15 years across all provinces. Cross tabulations and logistic regression were used to determine the prevalence and odds of the above disorders for each province. Adjustments for provincial sociodemographic factors were performed. Results: The past-year prevalence of all measured mental disorders and suicidality, excluding GAD, demonstrated significant interprovincial differences. Manitoba exhibited the highest prevalence of any mental disorder (13.6%), reflecting high prevalence of MDD and alcohol use disorder compared to the other provinces (7.0% and 3.8%, respectively). Nova Scotia exhibited the highest prevalence of substance use disorders (2.9%). Quebec and Prince Edward Island exhibited the lowest prevalence of any mental disorder (8.5% and 7.7%, respectively). Manitoba also exhibited the highest prevalence of suicidal ideation (5.1%); however, British Columbia and Ontario exhibited the highest prevalence of suicidal planning (1.4% and 1.3%, respectively), and Ontario alone exhibited the highest prevalence of suicide attempts (0.7%). Conclusions: Significant interprovincial differences were found in the past-year prevalence of mental disorders and suicidality in Canada. More research is necessary to explore these differences and how they impact the need for mental health services.
Salt intake is an essential dietary requirement, but excessive consumption is implicated in hypertension and associated conditions. Little is known about the neural circuit mechanisms that control motivation to consume salt, although the midbrain dopamine system, which plays a key role in other reward-related behaviors, has been implicated. We, therefore, examined the effects on salt consumption of either optogenetic excitation or chemogenetic inhibition of ventral tegmental area (VTA) dopamine neurons in male mice. Strikingly, optogenetic excitation of dopamine neurons decreased salt intake in a rapid and reversible manner, despite a strong salt appetite. Importantly, optogenetic excitation was not aversive, did not induce hyperactivity, and did not alter salt concentration preferences in a need-free state. In addition, we found that chemogenetic inhibition of dopamine neurons had no effect on salt intake. Lastly, optogenetic excitation of dopamine neurons reduced consumption of sucrose following an overnight fast, suggesting a more general role of VTA dopamine neuron excitation in organizing motivated behaviors.
IntroductionThe Canadian Chronic Disease Surveillance System (CCDSS) is a collaboration of provincial and territorial surveillance systems which generates estimates of chronic diseases using linked population-level administrative health databases and standard case definitions. We conducted an environmental scan of administrative data validation studies and identified opportunities for CCDSS case definition enhancement. Objectives and ApproachThe purpose of this project is to develop a methodology for and conduct an environmental scan, identifying opportunities for enhancing the CCDSS. This multifaceted approach consists of the following elements: 1) key informant interviews and stakeholder consultations to identify new and existing priority conditions for updating/validating within the CCDSS, and new areas of conceptual and methodological relevance for administrative data disease surveillance, 2) a systematic literature review of PubMed, Ovid and Embase from 2013-2017 using MeSH terms and a librarian peer-reviewed search strategy, and 3) a review of the grey literature. ResultsKey stakeholders identified the following priorities for validation work and/or case definition enhancement: diabetes, mood and anxiety disorders, schizophrenia, obesity, hypertension, chronic obstructive pulmonary disease, osteoarthritis, stroke, early-onset dementia, rheumatoid arthritis and gout. Scientific and grey literature reviews of validation work for these conditions examined the following concepts/methods: 1) evaluating validity of disease-specific case definitions over time, and in different ages, sub-populations and settings, 2) defining incidence versus prevalence using linked administrative data, 3) determining opportunities and constraints of using linked administrative data to conduct surveillance on diseases that are chronic versus episodic in nature and defining active versus lifetime prevalence, and 4) assessing the feasibility of using new sources of data for linkage to enhance case definition validity. Conclusion/ImplicationsUtilization of linked administrative databases for chronic disease surveillance has expanded across many jurisdictions since the inception of the CCDSS. As disease estimates generated in this manner are increasingly being relied upon by policy makers working to enhance public health, the methodological opportunities and constraints identified here require consideration.
IntroductionResearchers and decision makers from across Canada use linked provincial administrative data for analysis and to address research and policy questions. Currently there are several impediments to working harmoniously across provincial boundaries. A group of academic and policy researchers are working to address these multi-jurisdictional obstacles. Objectives and ApproachResearchers and data organizations from across Canada are working together as the Pan-Canadian Real-World Health Data Network PRHDN). PRHDN aims to: (1) create harmonized data, algorithms and analytic protocols, and (2) link administrative databases to other types of data, including electronic medical records, clinical trials records, “omics data” and records from pan-Canadian cohort studies. PRHDN’s vision is to construct a unified, documented infrastructure to advance pan-Canadian population-based research and analysis. This presentation incorporates material that is part of PRHDN’s response to a funding call to create national, collaborative infrastructure. ResultsScientists and staff at PRHDN organizations will create three main categories of infrastructure: 1) Algorithms: Reusable processes, ideally in the form of documented code, which implement a common approach or definition, e.g. to define cases or to create derived variables; 2) Harmonized Common Data: Based on the Sentinel model, we will establish a standardized subset of harmonized common data that are analysis-ready; 3) Common Analytic Protocols: Complementing work of the Canadian Network for Observational Drug Effect Studies (CNODES), we will establish processes for distributed analysis with common analytic protocols and meta-analysis of results to provide pan-Canadian estimates. Source data would remain within jurisdictional boundaries and only aggregate results would be pooled across jurisdictions. Details of these approaches will be presented. Conclusion/ImplicationsThis initiative will improve coordinated access to distributed data from across Canada that is built once then used by many stakeholders for a variety of purposes including: research, benchmarking, performance monitoring to identify gaps and opportunities for improvement, multi-jurisdictional evaluations of novel interventions and inter-jurisdictional comparisons.
Overall objectives or goal Most of the organizations that use population administrative data for research purposes have internal repository of validated definitions and algorithms of their own. Many of these concepts and definitions are applicable or at least adaptable to other organizations and jurisdictions. A comprehensive National (and potentially International) Concept Dictionary could help investigators to carry out methodologically sound work using consistent and validated algorithms using a shared pool of knowledge and resources. The Institute for Clinical Evaluative Sciences (ICES) in Ontario, Canada has recently modernized its internal Concept Dictionary by adopting standard templates based on the Manitoba Centre for Health Policy (MCHP) Concept Dictionary, reviewing and updating existing content and tagging the concept entries with appropriate MeSH terms and data sources, and adding standard computer code (e.g., SAS coding) where appropriate. A SharePoint® web-based application has been developed to provide advanced tagging, searching and browsing features. We envision a wiki-based Concept Dictionary hosted on a cloud-based environment with very granular access controls to provide enough flexibility for each participating organization to control their own content. This means each organization will be able to decide on how to share their own concepts (or part of them) with the public or internal users. All content will be tagged with MeSH terms and as well with the organization’s name that initially posts each entry. Other organizations which find the same concept applicable to their own use can tag the same entry with their organization name or refer to a secondary adapted entry if adaptation to fit their data and methodologies is required. The Search feature will allow refining the search criteria by MeSH terms, data sources, and also organization/jurisdiction name. Multiple layers of access controls will allow each organization to have their own groups of users with different standard privileges such as Local Administrators, Authors and Approvers (or Publishers). The Approver (Publisher) users within each organization can publish each entry for internal or public view. This way, for example, a definition/algorithm can be viewable only within the organization until the validation process is complete, and then the entry can be made publically available, while some sections, such as computer code, can remain restricted to the organization. We will discuss challenges in developing and maintaining such a platform including the costs, governance, intellectual property rights, copyrights and liabilities for the participating organizations. The intended output or outcome We aim to use this opportunity to form a working group from the interested organizations that are ready to participate and commit in developing this collaborative platform. After the conference, there will be follow up sessions with the members of the working group to plan and develop the online application.
BackgroundThere is growing recognition of the need for consistent and reliable reporting on mental health and addiction (MHA) services in Canada. While there have been improvements in the area of reporting within provinces, comparable measures across provinces are often confined to hospitalization data. The aim of this project was to test the feasibility of creating MHA performance indicators that could be compared across Canadian provinces. MethodsA team of scientists from five provinces collaboratively developed the following six MHA performance indicators for ages 10 and up, using hospital, emergency, physician billing and mortality data (pop. 33.2 million): Access to the same family physician for people with MHA problems First contact for MHA problems was in an emergency department Physician follow-up after hospitalization for MHA problems Rate of suicide attempts among people diagnosed with MHA problems Suicide rates among people diagnosed with MHA problems Mortality of people diagnosed with MHA problems To facilitate meaningful inter-provincial comparisons, consensus definitions and standardized analytic processes were developed. Within age groups, 95% CI’s were calculated to determine if there were significant differences across years within age bands. Results are presented in a comparative format. FindingsWe found similar patterns across provinces but significant variation in the absolute rates, with no province consistently best across all indicators. In general, outcomes were poor among adolescents and young adults compared to older groups. ConclusionsThe results of this pilot indicate the process is feasible and meaningful. Future work could include generating comparisons on a regular basis to track system improvement; development of other measures of importance to stakeholders; and the expansion of the process to other provinces and territories. To our knowledge, this is the first report of provincial teams working collaboratively to generate comparable data on the performance of mental health services in Canada.
Background Assertive community treatment for first-episode psychosis programs have been shown to improve symptoms and reduce service use. There is little or no evidence on whether these programs can increase access to income assistance and improve medication adherence in first episode psychosis patients. This research examines the impact of the Early Psychosis Prevention and Intervention Service (EPPIS) on these outcomes. Methods We extracted data on EPPIS patients held in the Data Repository at the Manitoba Centre for Health Policy. The Repository is a comprehensive collection of person-level de-identified administrative records, including data from Manitoba’s health services. We compared income assistance use and antipsychotic medication adherence in EPPIS patients to a historical cohort matched on pattern of diagnosis. Confounders were adjusted through propensity-score weighting with asymmetrical trimming. Odds ratios (OR), hazard ratios (HR) and 95% confidence intervals were calculated. Results We identified a matched sample of 244 patients and 449 controls. EPPIS patients had a higher rate of income assistance use during the program (67·4% vs. 38·7%; p< 0·0001). EPPIS patients were more likely to have been prescribed at least one antipsychotic medication than the control cohort, both during the program (OR = 15·05; 95%CI 10·81 to 20·94) and after the program ended (OR = 5·20; 95%CI: 4·50 to 6·02). Patients in EPPIS were also more likely to adhere to their medication during the program (OR = 4·71; 95%CI 3·75 to 5·92), and after the program (OR = 2·54; 95%CI 2·04 to 3·16). Conclusion Enrolment in the EPPIS program was associated with increased adherence to antipsychotic medication treatment and improved uptake of income assistance.
ABSTRACTObjectivesAn increasing number of physicians are remunerated by alternative forms of payment, instead of conventional fee-for-service (FFS) payments. Changes in physician remuneration methods can to influence the completeness of physician billing claims databases, because physicians on alternative payments may not consistently complete billing records. However, there is no established technique to estimate the magnitude of data loss. This proof-of-concept study estimated completeness of physician claims by comparing them with prescription drug records. We applied the method to estimate completeness of non-fee-for-service (NFFS) and FFS physician claims data over time in Manitoba, Canada. ApproachOur method uses information on the date of patient initiation of a new prescription medication, payment method of the prescribing physician, and presence/absence of a physician billing claim prior to the medication initiation date. A billing claim within 7 days of the medication initiation date was defined as a captured claim; if there was no claim in this observation window, it was classified as missed. Our method was applied to annual patient cohorts who initiated a common prescription medication (i.e., anti-hypertensives) between fiscal years 1998/99 and 2012/13. A sensitivity analysis used a 21-day observation window to identify captured/missing claims. Multivariable hierarchical logistic regression models tested patient and prescriber characteristics associated with missing claims. ResultsThe cohort consisted of 274, 462 individuals with a new anti-hypertensive prescription medication. A total of 9.2% of the cohort had a NFFS prescribing physician in 1998/99; this increased to 20.2% in 2012/13 (linear trend p-value < .0001). The percentage of NFFS prescribers almost doubled, from 10.0% to 17.8%. The percentage of the annual cohorts with a FFS prescribing physician and a missing claim remained close to 13.0%. However, the percentage of the annual cohorts with a NFFS prescribing physician and a missing claim increased from 15.6% to 23.3% (linear trend p-value < .0001), and was always higher than the FFS percentage. Patient age, sex, and comorbidity and physician specialty and practice location were associated with the odds of a missing claim. ConclusionThe percentage of missing claims was higher for patients with NFFS than FFS prescribing physicians, demonstrating the impact of physician remuneration on database completeness. The trend of greater data loss in later than earlier years suggests that completeness of physician billing claims data may be decreasing. Our method can be applied across jurisdictions to compare the impact of physician payment methods on data quality.
ABSTRACT Objective Fourteen years of social housing data (1995-2008) were acquired from the provincial government. This allowed for an unprecedented opportunity to describe the population of individuals living in social housing and, through data linkage, to compare them to the rest of the province on a number of health and social indicators. Approach Using data from the entire population of the province of Manitoba, Canada, cross-sectional comparison were made between those living in social housing and those not on 19 indicators of morbidity, mortality, health care utilization and social development. Regression models were developed to control for age, sex, region of residence, comorbidities, income and neighborhood level SES. Results 50% of the population in social housing are under the age 20, 75% are female and 50% of applicants receive some form of income assistance. As expected there are significant differences on most health status measures when compared to individuals not in social housing. However, after controlling for confounding factors most differences between the two groups disappear indicating that there is no independent effect of living in social housing. A few exceptions were noted on measures of total respiratory morbidity, mammography and high school completion rates, the later showing a very significant interaction with neighborhood level SES. Conclusion Despite overall poor health status, after controlling for income and other confounding factors individuals in social housing score no worse on many measures of health care utilization and prevention. High school completion rates, in particular, showed a very strong interaction with neighborhood level SES. Policy implications of this research are discussed.
Preclinical studies indicate that gonadal hormones are important determinants of drug self-administration. To date, little is known about the influence of sex and estrous cycle on drug self-administration in ecologically relevant social contexts.
The purpose of this study was to determine whether chronic exercise alters sensitivity to the conditioned rewarding effects of cocaine. Female rats were obtained at weaning and randomly assigned to either sedentary or exercise conditions. After 6 weeks under these conditions, the effects of cocaine were examined in the conditioned place preference procedure. Cocaine produced a dose-dependent conditioned place preference in both groups of rats. Exercising rats were more sensitive than sedentary rats to cocaine in this procedure, and this effect was most pronounced at the highest dose of cocaine. These data suggest that chronic exercise increases sensitivity to the conditioned rewarding effects of cocaine.
post-Soviet period. In the latter half of the 1990s, Moscow suggested a Russia-China-India strategic triangle as a counterweight to the USA. India had no interest in this idea. India and Russia probably did see each other as useful partners in verbally opposing US dominance, although India's relationship with the USA improved after the end of the Cold War. * Russo-Indian political cooperation has been good under Putin. Both have a strong interest in opposing Islamic terrorism. Russia probably also sees India as a useful means of checking Pakistani influence in Afghanistan and Central Asia. Russia supports India becoming a permanent member of the UN Security Council, and eventual membership for India and Pakistan of the