NMDA and dopamine interactions in the nucleus accumbens modulate cortical acetylcholine release

The nucleus accumbens (NAC) plays a key role in directing appropriate motor output following the presentation of behaviorally relevant stimuli. As such, we postulate that accumbens efferents also participate in the modulation of neuronal circuits regulating attentional processes directed toward the identification and selection of these stimuli. In this study, N -methyl-d-aspartate (NMDA) and D1 ligands were perfused into the shell region of the NAC of awake rats. Cortical cholinergic transmission, a mediator of attentional processes, was measured via microdialysis probes inserted into the prefrontal cortex (PFC). NMDA perfusions (150 or 250 µm) into NAC resulted in significant increases in acetylcholine (ACh) efflux in PFC (150–200% above baseline levels). Co-administration of the D1 antagonist SCH-23390 (150 µm) markedly attenuated (by approx. 70%) ACh efflux following perfusions of 150 µm NMDA but not following 250 µm NMDA, suggesting that D1 receptor activity contributes to the ability of the lower but not the higher concentration of NMDA to increase cortical ACh release. Collectively, these data reveal a positive modulation of NMDA receptors by D1 receptors in NAC that is expressed trans -synaptically at the level of cortical transmission. This modulation may underlie the coordinated linking of attentional processes and motor output following exposure to salient and behaviorally relevant stimuli.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72309/1/j.1460-9568.2005.04333.x.pd

An analysis of the global pharmacy workforce capacity trends from 2006 to 2012

Background: Human resources for health are at a critical low. The World Health Organization estimates that the current shortage of health workers, including pharmacists, is in excess of 7.2 million worldwide and that, by 2035,the shortage will reach 12.9 million. Pharmacists, in particular, are lacking in the workforce in many countries. The International Pharmaceutical Federation (FIP) and academic partners have conducted periodic global pharmacy workforce surveys in 2006, 2009 and 2012 which have monitored and reported on the status of the pharmacy workforce at the country and territory levels. This current analysis is a synthesis of workforce capacity data from these date points to provide an overview of the global trends and changes to pharmacy workforce capacity over this time period. Methods: The methodology proceeded with accessing workforce capacity data collated in 2006, 2009 and 2012 held on file at the FIP Collaborating Centre. This data had previously been validated and made available to WHO Human Resources for Health. The data focused (due to limitations from 2006 databank) on pharmacist workforce capacity. Countries and territories were identified that had data available across at least two of the three time points (2006, 2009 and 2012). Missing time-point data for some countries (data gaps) were subject, where possible, to literature and online data searching to capture possible missing data. Country-level capacity data were plotted against time to identify trends coupled with comparative analysis of the trends. Results: The countries and territories identified as having valid data for each of the time points 2006, 2009 and 2012 were present in all WHO regions, with Europe having the most countries with data available and South East Asia the fewest. All WHO regions have experienced an increase in the density of pharmacists (measured as number of pharmacists per 10 000 population) over the period 2006–2012. However, some countries show a reduction in the density of pharmacists. African countries show large relative increases in acceleration of capacity building but remain significantly behind in terms of absolute capacity per capita. South East Asian and Middle Eastern countries also show large proportional changes in pharmacist workforce. Conclusion: The global trend is an increase in workforce across all nations and regions, and this is a move in the right direction towards improved access to, and availability of, pharmaceutical expertise. However, there is still much to be done, with some regions and low-income countries still displaying a disproportionately low number of pharmacists on small overall capacity for delivering pharmacy service

Immigration Legislation and Issues in the 114th Congress

The House and the Senate have considered immigration measures on a variety of issues in the 114th Congress. The Consolidated Appropriations Act, 2016 (P.L. 114-113) extends four immigration programs through September 30, 2016: the EB-5 immigrant investor Regional Center Pilot Program, the E-Verify employment eligibility verification system, the Conrad State program for foreign medical graduates, and the special immigrant religious worker program. P.L. 114-113 also contains provisions on the Visa Waiver Program and certain nonimmigrant visa categories. Other enacted immigration-related measures include the Border Jobs for Veterans Act of 2015 (P.L. 114-68) on border security personnel, the Adoptive Family Relief Act (P.L. 114-70) on intercountry adoption, and the National Defense Authorization Act for Fiscal Year 2016 (P.L. 114-92) on the Afghan special immigrant visa program. The House has passed several other immigration-related bills. Among them are the Northern Border Security Review Act (H.R. 455), the Preclearance Authorization Act of 2015 (H.R. 998), the Border Security Technology Accountability Act of 2015 (H.R. 1634), the Enforce the Law for Sanctuary Cities Act (H.R. 3009), and the American SAFE Act of 2015 (H.R. 4038). H.R. 998 has also been reported by the Senate Homeland Security and Governmental Affairs Committee with an amendment in the nature of a substitute. In addition, various bills on border security, interior enforcement, visa security, and asylum, among other issues, have been considered by a House or Senate committee. Border security- related measures have been reported or ordered to be reported by the House Homeland Security Committee (H.R. 399, H.R. 3583, H.R. 3586), or the Senate Homeland Security and Governmental Affairs Committee (S. 750, S. 1808, S. 1864,S. 1873). Interior enforcement provisions are included in bills ordered to be reported by the House Judiciary Committee (H.R. 1147, H.R. 1148, H.R. 1153) or reported by the House Appropriations Committee (H.R. 3128). S. 1635, as reported by the Senate Foreign Relations Committee, also contains interior enforcement- related provisions. Several of these interior enforcement bills also contain key provisions on other immigration issues. Among the other issues addressed in these bills are employment eligibility verification (H.R. 1147); visa security and naturalization (H.R. 1148); and expedited removal, asylum, parole, and unaccompanied alien children (H.R. 1153). H.R. 1149, as ordered to be reported by the House Judiciary Committee, also addresses unaccompanied alien children. This report discusses these and other immigration-related issues that have received legislative action or are of significant congressional interest in the 114th Congress. Department of Homeland Security appropriations are addressed in CRS Report R44053, Department of Homeland Security Appropriations: FY2016, and, for the most part, are not covered here

An analysis of the global pharmacy workforce capacity

BACKGROUND: The World Health Organization (WHO) estimates that there is a global healthcare workforce shortage of 7.2 million, which is predicted to grow to 12.9 million by 2035. Globally, people are living longer with multiple co-morbidities and require increased access and use of medicines. Pharmacists are a key component of the healthcare workforce, and in many countries, pharmacists are the most accessible healthcare profession. This paper identifies key issues and current trends affecting the global pharmacy workforce, in particular workforce distribution, country economic status, capacity, and workforce gender balance. METHODS: National professional pharmacy leadership bodies, together with other contacts for professional bodies, regulatory bodies, and universities, were approached to provide country-level data on pharmacy workforce. A descriptive and comparative analysis was conducted to assess each country's pharmacy workforce. RESULTS: A total of 89 countries and territories responded to the survey. To standardise the capacity measure, an analysis of the population density of pharmacists (per 10 000 population) was performed. The sample mean was 6 pharmacists per 10 000 population (n = 80). There is considerable variation between the surveyed countries/territories ranging from 0.02 (Somalia) to 25.07 (Malta) pharmacists per 10 000 population. African nations have significantly fewer pharmacists per capita. Pharmacist density correlates with gross national income (GNI) and health expenditure. The majority of pharmacists are employed in community settings, followed by hospital, industry-related, academia, and regulation. There is a greater proportion of females in the pharmacy workforce globally, with some WHO regions showing female representation of more than 65 % with an increasing trend trajectory. CONCLUSIONS: Pharmacy workforce capacity varies considerably between countries and regions and generally correlates with population- and country-level economic indicators. Those countries and territories with lower economic indicators tend to have fewer pharmacists and pharmacy technicians; this has implications for inequalities regarding access to medicines and medicine expertise

Glacial and Postglacial Deposits of Northeastern Ohio

Author Institution: Department of Geology, University of AkronRecent high levels of Lake Erie have produced severe erosion and mass wasting along the shore. At the same time they have created excellent exposures of glacial and postglacial deposits east of Cleveland, Ohio. Glacial deposits consist of an older Coastal till and the Late Wisconsinan Ashtabula Till, whereas postglacial deposits generally are gravels, sands and silts. Lithofacies of the Ashtabula Till exposed at Sims Park in Euclid, Ohio, include sheared, massive diamicts and resedimented diamicts. The lowest sheared massive diamict previously identified as the Coastal till possibly represents a lodgement till deposited by Ashtabula ice. Beach deposits at Mentor Headlands resulted from construction of manmade structures. At Camp Isaac Jogues, deltaic sands overlie a sequence of diamicts, which has an unusually high carbonate content when compared to other sections along the shore. The geometry of the overlying sands and the facies sequence strongly suggest a river-dominated deltaic system. Two sand pits in beach ridges (one at the Warren level and the other at the Arkona level) farther inland contain coarse-grained facies that may represent an outwash plain or coastal barrier overlain by dune sand. A log dated at 13-4 ka was found at the Arkona level, 1 km south of the second pit

Immune Reactivity and Pseudoprogression or Tumor Flare in a Serially Biopsied Neuroendocrine Patient Treated with the Epigenetic Agent RRx-001.

Neuroendocrine tumors (NETs) are grouped together as a single class on the basis of histologic appearance, immunoreactivity for the neuroendocrine markers chromogranin A and synaptophysin, and potential secretion of hormones, neurotransmitters, neuromodulators and neuropeptides. Nevertheless, despite these common characteristics, NETs differ widely in terms of their natural histories: high-grade NETs are clinically aggressive and, like small cell lung cancer, which they most closely resemble, tend to respond to cisplatin and etoposide. In contrast, low-grade NETs, which as a rule progress and behave indolently, do not. In either case, the treatment strategy, apart from potentially curative surgical resection, is very poorly defined. This report describes the case of a 28-year-old white male with a diagnosis of high-grade NET of undetermined primary site metastatic to the lymph nodes, skin and paraspinal soft tissues, treated with the experimental anticancer agent RRx-001, in the context of a phase II clinical trial called TRIPLE THREAT (NCT02489903); serial sampling of tumor material through repeat biopsies demonstrated an intratumoral inflammatory response, including the amplification of infiltrating T cells, which correlated with clinical and symptomatic benefit. This case suggests that pseudoprogression or RRx-001-induced enlargement of tumor lesions, which has been previously described for several RRx-001-treated patients, is the result of tumoral lymphocyte infiltration

Acquisition of antibodies to merozoite surface protein 3 among residents of Korogwe, north eastern Tanzania

<p>Abstract</p> <p>Background</p> <p>A polymorphic malaria parasite antigen, merozoite surface protein 3 (MSP3), is among the blood stage malaria vaccine candidates. It is believed to induce immunity through cytophilic antibodies that disrupt the process of erythrocytes invasion by merozoites. This study aimed at assessing natural acquisition of antibodies to MSP3 in individuals living in an area with different malaria transmission intensity in preparation for malaria vaccine trials.</p> <p>Methods</p> <p>The study was conducted in individuals aged 0-19 years from villages located in lowland, intermediate and highland strata in Korogwe district, northeastern Tanzania. Blood samples from 492 study participants were collected between May and June 2006 for malaria diagnosis and immunological investigations. Reactivity of MSP3 to different types of antibodies (immunoglobulin M, G and IgG subclass 1 and 3) were analysed by Enzyme Linked ImmunoSorbent Assay (ELISA).</p> <p>Results</p> <p>Malaria parasite prevalence was higher in the lowland (50%) compared to the intermediate (23.1%) and highland (9.8%) strata. Immunogloblin G subclasses 1 and 3 (IgG1 & IgG3), total IgG and IgM were found to increase with increasing age. IgG3 levels were significantly higher than IgG1 (p < 0.001). Furthermore, <it>Plasmodium falciparum </it>infection was associated with higher IgG3 levels (p = 0.008). Adjusting by strata and age in individuals who had positive blood smears, both IgG and IgM were associated with parasite density, whereby IgG levels decreased by 0.227 (95%CI: 0.064 - 0.391; p = 0.007) while IgM levels decreased by 0.165 (95%CI: 0.044 - 0.286; p = 0.008).</p> <p>Conclusion</p> <p>Individuals with higher levels of IgG3 might be partially protected from malaria infection. Higher levels of total IgG and IgM in highlands might be due to low exposure to malaria infection, recent infection or presence of cross-reactive antigens. Further studies of longitudinal nature are recommended. Data obtained from this study were used in selection of one village (Kwashemshi) for conducting MSP3 phase 1b malaria vaccine trial in Korogwe.</p