Search

Your search keyword '"Anderson GM"' showing total 707 results
Start Over Author "Anderson GM"
707 results on '"Anderson GM"'

1. Long COVID-19 and Peripheral Serotonin: A Commentary and Reconsideration

Author

Anderson GM, Cook EH, Blakely RD, Sutcliffe JS, and Veenstra-VanderWeele J

Subjects
serotonin, covid-19, plasma, platelets, long-covid, viral infection, Pathology, RB1-214, Therapeutics. Pharmacology, RM1-950
Abstract

George M Anderson,1,2 Edwin H Cook,3 Randy D Blakely,4 James S Sutcliffe,5,6 Jeremy Veenstra-VanderWeele7,8 1Yale Child Study Center, Yale University School of Medicine, New Haven, CT, USA; 2Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, USA; 3Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA; 4FAU Stiles-Nicholson Brain Institute, Department of Biomedical Science, Florida Atlantic University, Jupiter, FL, USA; 5Department of Molecular Physiology & Biophysics, Vanderbilt University, Nashville, TN, USA; 6Department of Psychiatry & Behavioral Sciences, Vanderbilt University, Nashville, TN, USA; 7Department of Psychiatry, College of Medicine, Columbia University, New York, NY, USA; 8New York State Psychiatric Institute, Columbia University, New York, NY, USACorrespondence: George M Anderson, Yale Child Study Center, 230 S. Frontage Road, New Haven, CT, USA, Email george.anderson@yale.eduAbstract: We believe there are serious problems with a recently published and highly publicized paper entitled “Serotonin reduction in post-acute sequelae of viral infection.” The blood centrifugation procedure reportedly used by Wong et al would produce plasma that is substantially (over 95%) depleted of platelets. Given this, their published mean plasma serotonin values of 1.2 uM and 2.4 uM for the control/contrast groups appear to be at least 30 to 60 times too high and should be disregarded. The plasma serotonin values reported for the long COVID and viremia patients also should be disregarded, as should any comparisons to the control/contrast groups. We also note that the plasma serotonin means for the two control/contrast groups are not in good agreement. In the “Discussion” section, Wong et al state that their results tend to support the use of selective serotonin reuptake inhibitors (SSRIs) for the treatment of COVID-19, and they encourage further clinical trials of SSRIs. While they state that, “Our animal models demonstrate that serotonin levels can be restored and memory impairment reversed by precursor supplementation or SSRI treatment”, it should be noted that no data are presented showing an increase or restoration in circulating serotonin with SSRI administration. In fact, one would expect a marked decline in platelet serotonin due to SSRIs’ effective inhibition of the platelet serotonin transporter. Wong et al hypothesize that problems of long COVID arise from too little peripheral serotonin. However, given the frequent presence of a hyperaggregation state in long COVID, and the known augmenting effects of platelet serotonin on platelet aggregation, it is plausible to suggest that reductions in platelet serotonin might be associated with a lessening of the cardiovascular sequelae of COVID-19.Keywords: serotonin, COVID-19, plasma, platelets, long COVID, viral infection

Published
2024

2. Kisspeptin Neurones do not Directly Signal to RFRP‐3 Neurones but RFRP‐3 may Directly Modulate a Subset of Hypothalamic Kisspeptin Cells in Mice

Author

Poling, MC, Quennell, JH, Anderson, GM, and Kauffman, AS

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Contraception/Reproduction, Underpinning research, 1.1 Normal biological development and functioning, Animals, Female, Hypothalamus, In Situ Hybridization, Kisspeptins, Male, Mice, Mice, Inbred C57BL, Neurons, Neuropeptides, Receptors, G-Protein-Coupled, Signal Transduction, RFRP-3, Kiss1r, Gpr74, hypothalamus, neurokinin B, kisspeptin, Kiss1, Gpr147, Gpr54, reproduction, Tacr3, GnIH, Tac2, Endocrinology & Metabolism, Clinical sciences
Abstract

The neuropeptides kisspeptin (encoded by Kiss1) and RFamide-related peptide-3 (also known as GnIH; encoded by Rfrp) are potent stimulators and inhibitors, respectively, of reproduction. Whether kisspeptin or RFRP-3 might act directly on each other's neuronal populations to indirectly modulate reproductive status is unknown. To examine possible interconnectivity of the kisspeptin and RFRP-3 systems, we performed double-label in situ hybridisation (ISH) for the RFRP-3 receptors, Gpr147 and Gpr74, in hypothalamic Kiss1 neurones of adult male and female mice, as well as double-label ISH for the kisspeptin receptor, Kiss1r, in Rfrp-expressing neurones of the hypothalamic dorsal-medial nucleus (DMN). Only a very small proportion (5-10%) of Kiss1 neurones of the anteroventral periventricular region expressed Gpr147 or Gpr74 in either sex, whereas higher co-expression (approximately 25%) existed in Kiss1 neurones in the arcuate nucleus. Thus, RFRP-3 could signal to a small, primarily arcuate, subset of Kiss1 neurones, a conclusion supported by the finding of approximately 35% of arcuate kisspeptin cells receiving RFRP-3-immunoreactive fibre contacts. By contrast to the former situation, no Rfrp neurones co-expressed Kiss1r in either sex, and Tacr3, the receptor for neurokinin B (NKB; a neuropeptide co-expressed with arcuate kisspeptin neurones) was found in

Published
2013

5. Epithelial antibiotic induced in states of disease

Author

Robert H. Whitlock, Michael Zasloff, Stolzenberg Ed, Anderson Gm, and Ackermann Mr

Subjects
medicine.drug_class, Pasteurella Infections, Antimicrobial peptides, Antibiotics, Paratuberculosis, Bronchi, In situ hybridization, Biology, Epithelium, Microbiology, Defensins, Intestinal mucosa, medicine, Animals, Intestinal Mucosa, Mannheimia haemolytica, In Situ Hybridization, Lingual antimicrobial peptide, Multidisciplinary, Blood Proteins, Biological Sciences, respiratory system, medicine.disease, Mycobacterium avium subsp. paratuberculosis, Chronic infection, medicine.anatomical_structure, Immunology, Cattle
Abstract

Epithelial defensins provide an active defense against the external microbial environment. We investigated the distribution and expression of this class of antimicrobial peptides in normal cattle and in animals in varying states of disease. β-defensin mRNA was found to be widely expressed in numerous exposed epithelia but was found at higher levels in tissues that are constantly exposed to and colonized by microorganisms. We observed induction in ileal mucosa during chronic infection with Mycobacterium paratuberculosis and in bronchial epithelium after acute infection with Pasteurella haemolytica . It has been proposed that expression of antimicrobial peptides is an integral component of the inflammatory response. The results reported here support this hypothesis and suggest that epithelial defensins provide a rapidly mobilized local defense against infectious organisms.

Published
1997

13. Neighborhood income and stroke care and outcomes.

Author

Kapral MK, Fang J, Chan C, Alter DA, Bronskill SE, Hill MD, Manuel DG, Tu JV, Anderson GM, Kapral, Moira K, Fang, Jiming, Chan, Crystal, Alter, David A, Bronskill, Susan E, Hill, Michael D, Manuel, Douglas G, Tu, Jack V, and Anderson, Geoffrey M

Published
2012
Full Text
View/download PDF

17. Antipsychotic drugs and the risk of hyperglycemia in older adults without diabetes: a population-based observational study.

Author

Lipscombe LL, Lévesque LE, Gruneir A, Fischer HD, Juurlink DN, Gill SS, Herrmann N, Hux JE, Anderson GM, and Rochon PA

Abstract

OBJECTIVE: To determine whether current antipsychotic use among older persons without diabetes is associated with a higher risk of hospital visits for hyperglycemia, as previous studies in this population have yielded conflicting results. DESIGN, SETTING AND PARTICIPANTS: A nested case-control study within a population-based cohort of persons aged 66 years or older without diabetes, who initiated antipsychotic therapy between April 1, 2002, and March 31, 2006. Cohort members were identified using health databases from Ontario, Canada, and were followed from treatment start until March 31, 2007. MEASUREMENTS: Cases were patients with a hospital visit (emergency department visit or hospital admission) for hyperglycemia. We matched each case with up to 10 controls. We compared the risk of hyperglycemia among current antipsychotic users to that of remote users (discontinued > 180 days). RESULTS: The cohort consisted of 44,121 subjects, mean age of 78.3 years, followed for a mean of 2.2 years. Compared to remote antipsychotic use, current treatment with any antipsychotic was associated with a significantly increased risk of hospital visits for hyperglycemia (adjusted odds ratio [aOR]: 1.52; 95% confidence interval [CI]: 1.07-2.17). The risk was elevated for both atypical (aOR: 1.44; 95% CI: 1.01-2.07) and typical (aOR: 2.86; 95% CI: 1.46-5.59) antipsychotic agents. CONCLUSIONS: Current use of either atypical or typical antipsychotic agents was associated with a significantly increased risk of hospital visits for hyperglycemia among older persons without diabetes. These findings highlight the need for close glucose monitoring during antipsychotic therapy in older populations. [ABSTRACT FROM AUTHOR]

Published
2011
Full Text
View/download PDF

20. Frequency and pattern of emergency department visits by long-term care residents -- a population-based study.

Author

Gruneir A, Bell CM, Bronskill SE, Schull M, Anderson GM, and Rochon PA

Abstract

OBJECTIVES: To obtain population-based estimates of emergency department (ED) visits by long-term care (LTC) residents. DESIGN: Retrospective cohort study using administrative data. SETTING: All LTC facilities in Ontario, Canada. PARTICIPANTS: All LTC residents who visited an ED at least once during a 6-month period. MEASUREMENTS: All ED visits were described using the National Ambulatory Care Reporting System. Two distinct visit types were defined. Potentially preventable visits were defined as those for any ambulatory care sensitive condition; these are conditions for which exacerbations that result in hospital use suggest lack of access to adequate primary care. Low-acuity visits were defined as those triaged as nonurgent at ED registration and ended with return to the LTC facility without hospital admission. RESULTS: Nearly one-quarter of LTC residents visited the ED at least once in 6 months. Of all visits, 24.6% were for a potentially preventable reason, most commonly pneumonia, urinary tract infection, and congestive heart failure. These visits had a high frequency of ambulance transport (90.4%), emergent triage (35.3%), hospital admission (62.4%), and death within 30 days (23.6%). Of all visits, 11.0% were low acuity. Fall-related injury was the most common cause. Low-acuity visits were the shortest (mean length 4.5 ± 4.0 hours) and had the lowest frequency of death within 30 days (4.3%). CONCLUSION: LTC residents made frequent visits to the ED. The visit types showed distinct patterns that suggest a need for better access to medical care for common conditions and a greater emphasis on fall prevention in LTC. [ABSTRACT FROM AUTHOR]

Published
2010
Full Text
View/download PDF

26. Ferritin levels and their association with regional brain volumes in Tourette's syndrome.

Author

Gorman DA, Zhu H, Anderson GM, Davies M, Peterson BS, Gorman, Daniel A, Zhu, Hongtu, Anderson, George M, Davies, Mark, and Peterson, Bradley S

Abstract

Objective: A previous small study showed lower serum ferritin levels in subjects with Tourette's syndrome than in healthy subjects. The authors measured peripheral iron indices in a large group of Tourette's syndrome and comparison subjects and explored associations of ferritin levels with regional brain volumes.Method: Ferritin was measured in 107 children and adults (63 Tourette's syndrome, 44 comparison); serum iron was measured in 73 (41 Tourette's syndrome, 32 comparison). Magnetic resonance imaging scans were used to measure volumes of the basal ganglia and cortical gray matter.Results: Ferritin and serum iron were significantly lower in the Tourette's syndrome subjects, although still within the normal range. No association was found between tic severity and either iron index. In the Tourette's syndrome subjects, ferritin did not correlate significantly with caudate volume but did correlate positively with putamen volume. In the comparison subjects, ferritin correlated inversely with caudate volume but did not correlate significantly with putamen volume. Irrespective of diagnosis, ferritin correlated positively with volumes of the sensorimotor, midtemporal, and subgenual cortices.Conclusions: The lower peripheral ferritin and iron levels in persons with Tourette's syndrome are consistent with findings in other movement disorders and suggest that lower iron availability may have a causal role in the pathophysiology of tic disorders. Lower iron stores may contribute to hypoplasia of the caudate and putamen, increasing vulnerability to developing tics or to having more severe tics. Lower iron stores may also contribute to smaller cortical volumes and consequently to reduced inhibitory control of tics. [ABSTRACT FROM AUTHOR]

Published
2006
Full Text
View/download PDF

27. Trends in deliveries, prenatal care, and obstetrical complications in women with pregestational diabetes: a population-based study in Ontario, Canada, 1996-2001.

Author

Feig DS, Razzaq A, Sykora K, Hux JE, Anderson GM, Feig, Denice S, Razzaq, Asma, Sykora, Kathy, Hux, Jan E, and Anderson, Geoff M

Abstract

Objective: To describe recent trends in the proportion of deliveries in women with pregestational diabetes (PGD), their use of services, and diabetes-related obstetrical complications.Research Design and Methods: In this population-based retrospective cohort study, comprehensive administrative data were used to identify all women (with and without PGD) who gave birth in an Ontario, Canada, hospital from 1996 to 2001. Data on maternal complications and interventions were obtained from hospital discharge records; data on use of prenatal services were obtained from fee-for-service claims.Results: The proportion of deliveries in women with PGD increased steadily from 0.8% in 1996 to 1.2% in 2001 (P < 0.001). In 2001, women with PGD were more likely to be diagnosed with shoulder dystocia (adjusted odds ratio 2.00 [95% CI 1.55-2.58]), hypertension (4.13 [3.44-4.96]), and preeclampsia/eclampsia (4.44 [3.43-5.73]) and have higher rates of inductions (1.69 [1.52-1.88]) and caesarean sections (1.78 [1.60-1.98]) than women without PGD. In 2001, 50% of the women with PGD had a visit to a diabetes specialist during pregnancy and only 30% of women had claims for a prenatal retinal examination. Both of these rates have decreased over the study period.Conclusions: Women with PGD now account for a larger proportion of deliveries. These women continue to have higher obstetrical complication and intervention rates than women without PGD and many do not receive recommended specialty care during pregnancy. [ABSTRACT FROM AUTHOR]

Published
2006
Full Text
View/download PDF

28. Low-dose fluvoxamine treatment of children and adolescents with pervasive developmental disorders: a prospective, open-label study.

Author

Martin A, Koenig K, Anderson GM, and Scahill L

Abstract

The objective of this study was to assess the efficacy and tolerability of low-dose fluvoxamine (1.5 mg/kg/day) in youngsters with pervasive developmental disorders (PDDs). This was a prospective, open-label trial that included 18 subjects with a mean age of 11.3 +/- 3.6 years. Fourteen children (78%) completed the 10-week study. Premature discontinuation due to behavioral activation occurred in three participants. Although there was no response for the group as a whole, eight subjects (including all four females) were considered at least partial responders in intent-to-treat analyses. Neither pubertal status nor serotonin levels predicted clinical response. Fluvoxamine can be beneficial in the treatment of select children and adolescents with PDDs. Gender differences in selective serotonin reuptake inhibitor (SSRI) response warrant further investigation. [ABSTRACT FROM AUTHOR]

Published
2003
Full Text
View/download PDF

29. Trends in hospital use for mechanical neck and back problems in Ontario and the United States: discretionary care in different health care systems.

Author

Lavis JN, Malter A, Anderson GM, Taylor VM, Deyo RA, Bombardier C, Axcell T, and Kreuter W

Abstract

To describe and compare trends in hospital admission rates for mechanical neck and back problems between 1982 and 1992 in Ontario and the United States.~Objective~Objective~A descriptive analysis of hospital admissions, with data for Ontario extracted from the Canadian Institute for Health Information database and data for the US extracted from the National Hospital Discharge Survey.~Design~Methods~All acute care hospitals in Ontario and a probability sample of acute care hospitals in the US.~Setting~Methods~Adults aged 20 years or more who were admitted to an acute care hospital for mechanical neck or back problems in 1982, 1987 or 1992. Mechanical neck and back problems were defined using an algorithm developed by the study team.~Patients~Methods~Hospital admission rate per 100,000 adults.~Outcome Measure~Methods~Between 1982 and 1992 the hospital admission rate for medically treated cases decreased by 52% in Ontario and by 75% in the US. Over the same period the admission rate for surgically treated cases increased by 14% and by 35% respectively. By 1992 the admission rate for medically treated cases in the US was 23% higher than that in Ontario, whereas the rate for surgically treated cases was 164% higher.~Results~Results~The hospital-based medical or surgical treatment of mechanical neck and back problems provides an example of discretionary care. The higher admission rates for surgery in the US may reflect a larger supply of surgical specialists and imaging units. Further work is needed to confirm these findings for other types of discretionary care and to compare the appropriateness of care and clinical outcomes for discretionary care in these 2 jurisdictions.~Conclusions~Conclusions [ABSTRACT FROM AUTHOR]

Published
1998

34. Weight and leptin changes among risperidone-treated youths with autism: 6-month prospective data.

Author

Martin A, Scahill L, Anderson GM, Aman M, Arnold LE, McCracken J, McDougle CJ, Tierney E, Chuang S, Vitiello B, and Research Units on Pediatric Psychopharmacology Autism Network

Abstract

OBJECTIVE: The authors examined the developmental impact and temporal characteristics of risperidone-associated weight change. METHOD: Weight change was measured for 63 children and adolescents with autism treated with risperidone for 6 months. Change in serum leptin levels after 2 months was examined as a predictor of final weight gain in mixed regression models that controlled for site, gender, age, and risperidone dose. RESULTS: Age- and gender-standardized weight increased after 6 months of treatment (gross: mean=5.6 kg [SD=3.9]; standardized: mean=0.6 z [SD=0.5]) and was positively correlated with weight gained after 1 month. Change in leptin levels after 2 months of treatment (mean=-0.3 ng/ml, SD=6.2) (N=48) did not predict final weight gain. CONCLUSIONS: Chronic risperidone exposure in children with autism causes weight gain in excess of developmentally expected norms that follows a curvilinear trajectory and decelerates over time. Serum leptin change does not reliably predict risperidone-associated weight gain. [ABSTRACT FROM AUTHOR]

Published
2004
Full Text
View/download PDF

36. What is the quality of drug therapy clinical practice guidelines in Canada?

Author

Graham, Id, Beardall, S., Carter, Ao, Glennie, J., Hebert, Pc, Tetroe, Jm, Finlay McAlister, Visentin, S., and Anderson, Gm

Subjects
Canada, Databases, Factual, Drug Therapy, Research, Practice Guidelines as Topic, Humans, Letters
Abstract

The Canadian Medical Association maintains a national online database of clinical practice guidelines developed, endorsed or reviewed by Canadian organizations within 5 years of the current date. This study was designed to identify and describe guidelines in the database that make recommendations related to the use of drug therapy, and to assess their quality using a standardized guideline appraisal instrument.Drug therapy guidelines in the database were identified with the use of search terms and hand searching. Descriptive information about the developers, endorsement by other organizations, publication status, disease and drug focus was abstracted. Each guideline was independently assessed by 3 appraisers (a physician, a pharmacist and a methodologist) with the use of the Appraisal Instrument for Clinical Guidelines. Conditions were classified according to the tenth revision of the International Statistical Classification of Diseases and Related Health Problems.We identified 217 drug therapy guidelines produced or reviewed from 1994 to 1998. Guideline developers included national organizations (47.0%), paragovernment organizations (39.6%) and professional associations (30.9%); 31.3% of the guidelines were published, and 10.6% stated drug company sponsorship. The most common conditions addressed by the guidelines were infections and parasitic diseases (39.6%), neoplasms (11.5%) and diseases of the circulatory system (11.5%). Drugs most commonly cited were anti-infective agents (42.9%), antiviral agents (15.2%) and cardiovascular drugs (16.1%). Eleven organizations produced 176 (81.1%) of the guidelines. In all, 14.7% of the guidelines met half or more of the 20 items assessing rigour of guideline development on the appraisal instrument (mean quality score 30.0% [95% confidence interval (CI) 27.5%-32.6%]), 61.8% met half or more of the 12 items assessing guideline context and content (mean score 57.0% [95% CI 54.6%-59.3%]), and none met half or more of the 5 items assessing guideline application (mean score 5.6% [95% CI 4.7%-6.5%]). Overall, 64.6% of the guidelines were recommended with modification by at least 2 of the 3 appraisers, 9.2% were recommended without change, and 26.3% were not recommended. The quality of the guidelines assessed varied significantly by developer, publication status and drug company sponsorship. No substantial improvement in guideline quality was observed over the 5-year study period.Developers of Canadian drug therapy guidelines are producing guidelines that are often perceived to be clinically useful to physicians and pharmacists, although the methods (or the description of the methods) by which they are developed need to be more rigorous and thorough.

39. Plasma kynurenine and related measures in tic disorder patients.

Author

Hoekstra PJ, Anderson GM, Troost PW, Kallenberg CGM, and Minderaa RB

Abstract

OBJECTIVE: Increased plasma kynurenine has been reported in tic disorder patients, and this observation has been suggested to be indicative of immune dysregulation. In the present study, we examined plasma levels of kynurenine and related molecules in a group of tic disorder patients. METHODS: Plasma concentrations of tryptophan, kynurenine, cortisol, and neopterin were determined in Dutch tic disorder patients (N = 59), and healthy volunteers (N = 32). Group means were compared and age-controlled intra-individual correlations between tic severity and plasma levels of these molecules were examined. RESULTS: No significant differences were found between patient and control groups in plasma levels of tryptophan, kynurenine, and cortisol concentrations, nor in the kynurenine/tryptophan ratio. However, neopterin was significantly (p = 0.035) higher in patients (mean = 5.13 nmol/l) than in controls (mean = 3.30 nmol/l). Plasma levels of these molecules did not correlate with tic severity, with the exception of tryptophan (r = -0.289, p = 0.049). In patients, plasma neopterin correlated with kynurenine (r = 0.438, p = 0.002); in healthy subjects, tryptophan correlated with kynurenine (r = 0.670, p < 0.001). CONCLUSION: While the observed elevation in plasma neopterin is consistent with immune activation in a subset of tic disorder patients, metabolism of tryptophan through the kynurenine pathway appears to be unaltered in tic disorder patients. [ABSTRACT FROM AUTHOR]

Published
2007

43. Temporal trends in general and age-specific fertility rates among women with schizophrenia (1996-2009): a population-based study in Ontario, Canada.

Author

Vigod SN, Seeman MV, Ray JG, Anderson GM, Dennis CL, Grigoriadis S, Gruneir A, Kurdyak PA, Rochon PA, Vigod, Simone N, Seeman, Mary V, Ray, Joel G, Anderson, Geoffrey M, Dennis, Cindy Lee, Grigoriadis, Sophie, Gruneir, Andrea, Kurdyak, Paul A, and Rochon, Paula A

Abstract

Purpose: There is substantial evidence that women with schizophrenia in many parts of the world have fewer children than their peers. Our objective was to analyze recent trends in general and age-specific fertility rates among women with schizophrenia in Ontario, Canada.Methods: We conducted a repeated cross-sectional population-based study from 1996 to 2009 using population-based linked administrative databases for the entire province of Ontario. Women aged 15-49 years were classified into schizophrenia and non-schizophrenia groups in each successive 12-month period. Annual general and age-specific fertility rates were derived.Results: The general fertility rate (GFR) among women with schizophrenia was 1.16 times higher in 2007-2009 than in 1996-1998 (95% confidence interval [CI] 1.04-1.31). The annual GFR ratio of women with vs. without schizophrenia was 0.41 (95% CI 0.36-0.47) in 2009, which was slightly higher than the same ratio in 1996 of 0.30 (95% CI 0.25-0.35). Annual age-specific fertility rates (ASFR) increased over time among women with schizophrenia aged 20-24, 25-29, 35-39 and 40-44 years, but the increase was not always statistically significant. Among women aged 20-24 years, the ASFR ratio in women with vs. without schizophrenia was not significant by the end of the study period (0.93, 95% CI 0.70-1.22).Conclusions: The general fertility rate among women with schizophrenia appears to have increased modestly over the past 13 years. Clinical care and health policy should consider new strategies that focus on the mental health of women with schizophrenia as new mothers, while optimizing healthy pregnancies and child rearing. [ABSTRACT FROM AUTHOR]

Published
2012
Full Text
View/download PDF

44. International report: using pharmacoepidemiology to inform drug coverage policy: initial lessons from a two-province collaborative: which evidence matters the most to drug plan manager?

Author

Paterson JM, Laupacis A, Bassett K, Anderson GM, and BC-Ontario Pharmacosurveillance for Decision-Making Collaborative

Abstract

Prescription drug plan managers seek 'real-world' evidence regarding the safety and effectiveness of drugs and drug coverage policies. University-based pharmacoepidemiologists with access to administrative health data can help meet these information needs and, by collaborating with other health plans, exploit variations in plan policy. Canada, with its universal health insurance, public drug benefit plans, and population-based linked health care databases, is an ideal setting for such research. Here we describe our initial experience in collaborating with researchers and drug plan managers in British Columbia and Ontario. [ABSTRACT FROM AUTHOR]

Published
2006
Full Text
View/download PDF

45. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015

Author

Vos, Theo, Allen, Christine, Arora, Megha, Barber, Ryan M, Bhutta, Zulfiqar A, Brown, Alexandria, Carter, Austin, Casey, Daniel C, Charlson, Fiona J, Chen, Alan Z, Coggeshall, Megan, Cornaby, Leslie, Dandona, Lalit, Dicker, Daniel J, Dilegge, Tina, Erskine, Holly E, Ferrari, Alize J, Fitzmaurice, Christina, Fleming, Tom, Forouzanfar, Mohammad H, Fullman, Nancy, Gething, Peter W, Goldberg, Ellen M, Graetz, Nicholas, Haagsma, Juanita A, Hay, Simon I, Johnson, Catherine O, Kassebaum, Nicholas J, Kawashima, Toana, Kemmer, Laura, Khalil, Ibrahim A, Kinfu, Yohannes, Kyu, Hmwe H, Leung, Janni, Liang, Xiaofeng, Lim, Stephen S, Lopez, Alan D, Lozano, Rafael, Marczak, Laurie, Mensah, George A, Mokdad, Ali H, Naghavi, Mohsen, Nguyen, Grant, Nsoesie, Elaine, Olsen, Helen, Pigott, David M, Pinho, Christine, Rankin, Zane, Reinig, Nikolas, Salomon, Joshua A, Sandar, Logan, Smith, Alison, Stanaway, Jeffrey, Steiner, Caitlyn, Teeple, Stephanie, Thomas, Bernadette A, Troeger, Christopher, Wagner, Joseph A, Wang, Haidong, Wanga, Valentine, Whiteford, Harvey A, Zoeckler, Leo, Abajobir, Amanuel Alemu, Abate, Kalkidan Hassen, Abbafati, Cristiana, Abbas, Kaja M, Abd-Allah, Foad, Abraham, Biju, Abubakar, Ibrahim, Abu-Raddad, Laith J, Abu-Rmeileh, Niveen M E, Ackerman, Ilana N, Adebiyi, Akindele Olupelumi, Ademi, Zanfina, Adou, Arsène Kouablan, Afanvi, Kossivi Agbelenko, Agardh, Emilie Elisabet, Agarwal, Arnav, Kiadaliri, Aliasghar Ahmad, Ahmadieh, Hamid, Ajala, Oluremi N, Akinyemi, Rufus Olusola, Akseer, Nadia, Al-Aly, Ziyad, Alam, Khurshid, Alam, Noore K M, Aldhahri, Saleh Fahed, Alegretti, Miguel Angel, Alemu, Zewdie Aderaw, Alexander, Lily T, Alhabib, Samia, Ali, Raghib, Alkerwi, Ala'a, Alla, François, Allebeck, Peter, Al-Raddadi, Rajaa, Alsharif, Ubai, Altirkawi, Khalid A, Alvis-Guzman, Nelson, Amare, Azmeraw T, Amberbir, Alemayehu, Amini, Heresh, Ammar, Walid, Amrock, Stephen Marc, Andersen, Hjalte H, Anderson, Gregory M, Anderson, Benjamin O, Antonio, Carl Abelardo T, Aregay, Atsede Fantahun, Ärnlöv, Johan, Artaman, Al, Asayesh, Hamid, Assadi, Reza, Atique, Suleman, Avokpaho, Euripide Frinel G Arthur, Awasthi, Ashish, Quintanilla, Beatriz Paulina Ayala, Azzopardi, Peter, Bacha, Umar, Badawi, Alaa, Balakrishnan, Kalpana, Banerjee, Amitava, Barac, Aleksandra, Barker-Collo, Suzanne L, Bärnighausen, Till, Barregard, Lars, Barrero, Lope H, Basu, Arindam, Bazargan-Hejazi, Shahrzad, Beghi, Ettore, Bell, Brent, Bell, Michelle L, Bennett, Derrick A, Bensenor, Isabela M, Benzian, Habib, Berhane, Adugnaw, Bernabé, Eduardo, Betsu, Balem Demtsu, Beyene, Addisu Shunu, Bhala, Neeraj, Bhatt, Samir, Biadgilign, Sibhatu, Bienhoff, Kelly, Bikbov, Boris, Biryukov, Stan, Bisanzio, Donal, Bjertness, Espen, Blore, Jed, Borschmann, Rohan, Boufous, Soufiane, Brainin, Michael, Brazinova, Alexandra, Breitborde, Nicholas J K, Brown, Jonathan, Buchbinder, Rachelle, Buckle, Geoffrey Colin, Butt, Zahid A, Calabria, Bianca, Campos-Nonato, Ismael Ricardo, Campuzano, Julio Cesar, Carabin, Hélène, Cárdenas, Rosario, Carpenter, David O, Carrero, Juan Jesus, Castañeda-Orjuela, Carlos A, Rivas, Jacqueline Castillo, Catalá-López, Ferrán, Chang, Jung-Chen, Chiang, Peggy Pei-Chia, Chibueze, Chioma Ezinne, Chisumpa, Vesper Hichilombwe, Choi, Jee-Young Jasmine, Chowdhury, Rajiv, Christensen, Hanne, Christopher, Devasahayam Jesudas, Ciobanu, Liliana G, Cirillo, Massimo, Coates, Matthew M, Colquhoun, Samantha M, Cooper, Cyrus, Cortinovis, Monica, Crump, John A, Damtew, Solomon Abrha, Dandona, Rakhi, Daoud, Farah, Dargan, Paul I, das Neves, José, Davey, Gail, Davis, Adrian C, Leo, Diego De, Degenhardt, Louisa, Gobbo, Liana C Del, Dellavalle, Robert P, Deribe, Kebede, Deribew, Amare, Derrett, Sarah, Jarlais, Don C Des, Dharmaratne, Samath D, Dhillon, Preet K, Diaz-Torné, Cesar, Ding, Eric L, Driscoll, Tim R, Duan, Leilei, Dubey, Manisha, Duncan, Bruce Bartholow, Ebrahimi, Hedyeh, Ellenbogen, Richard G, Elyazar, Iqbal, Endres, Matthias, Endries, Aman Yesuf, Ermakov, Sergey Petrovich, Eshrati, Babak, Estep, Kara, Farid, Talha A, Farinha, Carla Sofia e Sa, Faro, André, Farvid, Maryam S, Farzadfar, Farshad, Feigin, Valery L, Felson, David T, Fereshtehnejad, Seyed-Mohammad, Fernandes, Jefferson G, Fernandes, Joao C, Fischer, Florian, Fitchett, Joseph R A, Foreman, Kyle, Fowkes, F Gerry R, Fox, Jordan, Franklin, Richard C, Friedman, Joseph, Frostad, Joseph, Fürst, Thomas, Futran, Neal D, Gabbe, Belinda, Ganguly, Parthasarathi, Gankpé, Fortuné Gbètoho, Gebre, Teshome, Gebrehiwot, Tsegaye Tewelde, Gebremedhin, Amanuel Tesfay, Geleijnse, Johanna M, Gessner, Bradford D, Gibney, Katherine B, Ginawi, Ibrahim Abdelmageem Mohamed, Giref, Ababi Zergaw, Giroud, Maurice, Gishu, Melkamu Dedefo, Giussani, Giorgia, Glaser, Elizabeth, Godwin, William W, Gomez-Dantes, Hector, Gona, Philimon, Goodridge, Amador, Gopalani, Sameer Vali, Gotay, Carolyn C, Goto, Atsushi, Gouda, Hebe N, Grainger, Rebecca, Greaves, Felix, Guillemin, Francis, Guo, Yuming, Gupta, Rahul, Gupta, Rajeev, Gupta, Vipin, Gutiérrez, Reyna A, Haile, Demewoz, Hailu, Alemayehu Desalegne, Hailu, Gessessew Bugssa, Halasa, Yara A, Hamadeh, Randah Ribhi, Hamidi, Samer, Hammami, Mouhanad, Hancock, Jamie, Handal, Alexis J, Hankey, Graeme J, Hao, Yuantao, Harb, Hilda L, Harikrishnan, Sivadasanpillai, Haro, Josep Maria, Havmoeller, Rasmus, Hay, Roderick J, Heredia-Pi, Ileana Beatriz, Heydarpour, Pouria, Hoek, Hans W, Horino, Masako, Horita, Nobuyuki, Hosgood, H Dean, Hoy, Damian G, Htet, Aung Soe, Huang, Hsiang, Huang, John J, Huynh, Chantal, Iannarone, Marissa, Iburg, Kim Moesgaard, Innos, Kaire, Inoue, Manami, Iyer, Veena J, Jacobsen, Kathryn H, Jahanmehr, Nader, Jakovljevic, Mihajlo B, Javanbakht, Mehdi, Jayaraman, Sudha P, Jayatilleke, Achala Upendra, Jee, Sun Ha, Jeemon, Panniyammakal, Jensen, Paul N, Jiang, Ying, Jibat, Tariku, Jimenez-Corona, Aida, Jin, Ye, Jonas, Jost B, Kabir, Zubair, Kalkonde, Yogeshwar, Kamal, Ritul, Kan, Haidong, Karch, André, Karema, Corine Kakizi, Karimkhani, Chante, Kasaeian, Amir, Kaul, Anil, Kawakami, Norito, Keiyoro, Peter Njenga, Kemp, Andrew Haddon, Keren, Andre, Kesavachandran, Chandrasekharan Nair, Khader, Yousef Saleh, Khan, Abdur Rahman, Khan, Ejaz Ahmad, Khang, Young-Ho, Khera, Sahil, Khoja, Tawfik Ahmed Muthafer, Khubchandani, Jagdish, Kieling, Christian, Kim, Pauline, Kim, Cho-il, Kim, Daniel, Kim, Yun Jin, Kissoon, Niranjan, Knibbs, Luke D, Knudsen, Ann Kristin, Kokubo, Yoshihiro, Kolte, Dhaval, Kopec, Jacek A, Kosen, Soewarta, Kotsakis, Georgios A, Koul, Parvaiz A, Koyanagi, Ai, Kravchenko, Michael, Defo, Barthelemy Kuate, Bicer, Burcu Kucuk, Kudom, Andreas A, Kuipers, Ernst J, Kumar, G Anil, Kutz, Michael, Kwan, Gene F, Lal, Aparna, Lalloo, Ratilal, Lallukka, Tea, Lam, Hilton, Lam, Jennifer O, Langan, Sinead M, Larsson, Anders, Lavados, Pablo M, Leasher, Janet L, Leigh, James, Leung, Ricky, Levi, Miriam, Li, Yichong, Li, Yongmei, Liang, Juan, Liu, Shiwei, Liu, Yang, Lloyd, Belinda K, Lo, Warren D, Logroscino, Giancarlo, Looker, Katharine J, Lotufo, Paulo A, Lunevicius, Raimundas, Lyons, Ronan A, Mackay, Mark T, Magdy, Mohammed, Razek, Abd El, Mahdavi, Mahdi, Majdan, Marek, Majeed, Azeem, Malekzadeh, Reza, Marcenes, Wagner, Margolis, David Joel, Martinez-Raga, Jose, Masiye, Felix, Massano, João, McGarvey, Stephen Theodore, McGrath, John J, McKee, Martin, McMahon, Brian J, Meaney, Peter A, Mehari, Alem, Mejia-Rodriguez, Fabiola, Mekonnen, Alemayehu B, Melaku, Yohannes Adama, Memiah, Peter, Memish, Ziad A, Mendoza, Walter, Meretoja, Atte, Meretoja, Tuomo J, Mhimbira, Francis Apolinary, Millear, Anoushka, Miller, Ted R, Mills, Edward J, Mirarefin, Mojde, Mitchell, Philip B, Mock, Charles N, Mohammadi, Alireza, Mohammed, Shafiu, Monasta, Lorenzo, Hernandez, Julio Cesar Montañez, Montico, Marcella, Mooney, Meghan D, Moradi-Lakeh, Maziar, Morawska, Lidia, Mueller, Ulrich O, Mullany, Erin, Mumford, John Everett, Murdoch, Michele E, Nachega, Jean B, Nagel, Gabriele, Naheed, Aliya, Naldi, Luigi, Nangia, Vinay, Newton, John N, Ng, Marie, Ngalesoni, Frida Namnyak, Nguyen, Quyen Le, Nisar, Muhammad Imran, Pete, Patrick Martial Nkamedjie, Nolla, Joan M, Norheim, Ole F, Norman, Rosana E, Norrving, Bo, Nunes, Bruno P, Ogbo, Felix Akpojene, Oh, In-Hwan, Ohkubo, Takayoshi, Olivares, Pedro R, Olusanya, Bolajoko Olubukunola, Olusanya, Jacob Olusegun, Ortiz, Alberto, Osman, Majdi, Ota, Erika, PA, Mahesh, Park, Eun-Kee, Parsaeian, Mahboubeh, de Azeredo Passos, Valéria Maria, Caicedo, Angel J Paternina, Patten, Scott B, Patton, George C, Pereira, David M, Perez-Padilla, Rogelio, Perico, Norberto, Pesudovs, Konrad, Petzold, Max, Phillips, Michael Robert, Piel, Frédéric B, Pillay, Julian David, Pishgar, Farhad, Plass, Dietrich, Platts-Mills, James A, Polinder, Suzanne, Pond, Constance D, Popova, Svetlana, Poulton, Richie G, Pourmalek, Farshad, Prabhakaran, Dorairaj, Prasad, Noela M, Qorbani, Mostafa, Rabiee, Rynaz H S, Radfar, Amir, Rafay, Anwar, Rahimi, Kazem, Rahimi-Movaghar, Vafa, Rahman, Mahfuzar, Rahman, Mohammad Hifz Ur, Rahman, Sajjad Ur, Rai, Rajesh Kumar, Rajsic, Sasa, Ram, Usha, Rao, Puja, Refaat, Amany H, Reitsma, Marissa B, Remuzzi, Giuseppe, Resnikoff, Serge, Reynolds, Alex, Ribeiro, Antonio L, Blancas, Maria Jesus Rios, Roba, Hirbo Shore, Rojas-Rueda, David, Ronfani, Luca, Roshandel, Gholamreza, Roth, Gregory A, Rothenbacher, Dietrich, Roy, Ambuj, Sagar, Rajesh, Sahathevan, Ramesh, Sanabria, Juan R, Sanchez-Niño, Maria Dolores, Santos, Itamar S, Santos, João Vasco, Sarmiento-Suarez, Rodrigo, Sartorius, Benn, Satpathy, Maheswar, Savic, Miloje, Sawhney, Monika, Schaub, Michael P, Schmidt, Maria Inês, Schneider, Ione J C, Schöttker, Ben, Schwebel, David C, Scott, James G, Seedat, Soraya, Sepanlou, Sadaf G, Servan-Mori, Edson E, Shackelford, Katya A, Shaheen, Amira, Shaikh, Masood Ali, Sharma, Rajesh, Sharma, Upasana, Shen, Jiabin, Shepard, Donald S, Sheth, Kevin N, Shibuya, Kenji, Shin, Min-Jeong, Shiri, Rahman, Shiue, Ivy, Shrime, Mark G, Sigfusdottir, Inga Dora, Silva, Diego Augusto Santos, Silveira, Dayane Gabriele Alves, Singh, Abhishek, Singh, Jasvinder A, Singh, Om Prakash, Singh, Prashant Kumar, Sivonda, Anna, Skirbekk, Vegard, Skogen, Jens Christoffer, Sligar, Amber, Sliwa, Karen, Soljak, Michael, Søreide, Kjetil, Sorensen, Reed J D, Soriano, Joan B, Sposato, Luciano A, Sreeramareddy, Chandrashekhar T, Stathopoulou, Vasiliki, Steel, Nicholas, Stein, Dan J, Steiner, Timothy J, Steinke, Sabine, Stovner, Lars, Stroumpoulis, Konstantinos, Sunguya, Bruno F, Sur, Patrick, Swaminathan, Soumya, Sykes, Bryan L, Szoeke, Cassandra E I, Tabarés-Seisdedos, Rafael, Takala, Jukka S, Tandon, Nikhil, Tanne, David, Tavakkoli, Mohammad, Taye, Bineyam, Taylor, Hugh R, Ao, Braden J Te, Tedla, Bemnet Amare, Terkawi, Abdullah Sulieman, Thomson, Alan J, Thorne-Lyman, Andrew L, Thrift, Amanda G, Thurston, George D, Tobe-Gai, Ruoyan, Tonelli, Marcello, Topor-Madry, Roman, Topouzis, Fotis, Tran, Bach Xuan, Truelsen, Thomas, Dimbuene, Zacharie Tsala, Tsilimbaris, Miltiadis, Tura, Abera Kenay, Tuzcu, Emin Murat, Tyrovolas, Stefanos, Ukwaja, Kingsley N, Undurraga, Eduardo A, Uneke, Chigozie Jesse, Uthman, Olalekan A, van Gool, Coen H, Varakin, Yuri Y, Vasankari, Tommi, Venketasubramanian, Narayanaswamy, Verma, Raj Kumar, Violante, Francesco S, Vladimirov, Sergey K, Vlassov, Vasiliy Victorovich, Vollset, Stein Emil, Wagner, Gregory R, Waller, Stephen G, Wang, Linhong, Watkins, David A, Weichenthal, Scott, Weiderpass, Elisabete, Weintraub, Robert G, Werdecker, Andrea, Westerman, Ronny, White, Richard A, Williams, Hywel C, Wiysonge, Charles Shey, Wolfe, Charles D A, Won, Sungho, Woodbrook, Rachel, Wubshet, Mamo, Xavier, Denis, Xu, Gelin, Yadav, Ajit Kumar, Yan, Lijing L, Yano, Yuichiro, Yaseri, Mehdi, Ye, Pengpeng, Yebyo, Henock Gebremedhin, Yip, Paul, Yonemoto, Naohiro, Yoon, Seok-Jun, Younis, Mustafa Z, Yu, Chuanhua, Zaidi, Zoubida, Zaki, Maysaa El Sayed, Zeeb, Hajo, Zhou, Maigeng, Zodpey, Sanjay, Zuhlke, Liesl Joanna, Murray, Christopher J L, Vos, T, Allen, C, Arora, M, Barber, Rm, Bhutta, Za, Brown, A, Carter, A, Casey, Dc, Charlson, Fj, Chen, Az, Coggeshall, M, Cornaby, L, Dandona, L, Dicker, Dj, Dilegge, T, Erskine, He, Ferrari, Aj, Fitzmaurice, C, Fleming, T, Forouzanfar, Mh, Fullman, N, Gething, Pw, Goldberg, Em, Graetz, N, Haagsma, Ja, Johnson, Co, Kassebaum, Nj, Kawashima, T, Kemmer, L, Khalil, Ia, Kinfu, Y, Kyu, Hh, Leung, J, Liang, X, Lim, S, Lopez, Ad, Lozano, R, Marczak, L, Mensah, Ga, Mokdad, Ah, Naghavi, M, Nguyen, G, Nsoesie, E, Olsen, H, Pigott, Dm, Pinho, C, Rankin, Z, Reinig, N, Salomon, Ja, Sandar, L, Smith, A, Stanaway, J, Steiner, C, Teeple, S, Thomas, Ba, Troeger, C, Wagner, Ja, Wang, H, Wanga, V, Whiteford, Ha, Zoeckler, L, Abajobir, Aa, Abate, Kh, Abbafati, C, Abbas, Km, Abd Allah, F, Abraham, B, Abubakar, I, Abu Raddad, Lj, Abu Rmeileh, Nm, Ackerman, In, Adebiyi, Ao, Ademi, Z, Adou, Ak, Afanvi, Ka, Agardh, Ee, Agarwal, A, Kiadaliri, Aa, Ahmadieh, H, Ajala, On, Akinyemi, Ro, Akseer, N, Al Aly, Z, Alam, K, Alam, Nk, Aldhahri, Sf, Alegretti, Ma, Alemu, Za, Alexander, Lt, Alhabib, S, Ali, R, Alkerwi, A, Alla, F, Allebeck, P, Al Raddadi, R, Alsharif, U, Altirkawi, Ka, Alvis Guzman, N, Amare, At, Amberbir, A, Amini, H, Ammar, W, Amrock, Sm, Andersen, Hh, Anderson, Gm, Anderson, Bo, Antonio, Ca, Aregay, Af, Ärnlöv, J, Artaman, A, Asayesh, H, Assadi, R, Atique, S, Avokpaho, Ef, Awasthi, A, Quintanilla, Bp, Azzopardi, P, Bacha, U, Badawi, A, Balakrishnan, K, Banerjee, A, Barac, A, Barker Collo, Sl, Bärnighausen, T, Barregard, L, Barrero, Lh, Basu, A, Bazargan Hejazi, S, Bell, B, Bell, Ml, Bennett, Da, Bensenor, Im, Benzian, H, Berhane, A, Bernabé, E, Betsu, Bd, Beyene, A, Bhala, N, Bhatt, S, Biadgilign, S, Bienhoff, K, Bikbov, B, Biryukov, S, Bisanzio, D, Bjertness, E, Blore, J, Borschmann, R, Boufous, S, Brainin, M, Brazinova, A, Breitborde, Nj, Brown, J, Buchbinder, R, Buckle, Gc, Butt, Za, Calabria, B, Campos Nonato, Ir, Campuzano, Jc, Carabin, H, Cárdenas, R, Carpenter, Do, Carrero, Jj, Castañeda Orjuela, Ca, Rivas, Jc, Catalá López, F, Chang, Jc, Chiang, Pp, Chibueze, Ce, Chisumpa, Vh, Choi, Jj, Chowdhury, R, Christensen, H, Christopher, Dj, Ciobanu, Lg, Cirillo, Massimo, Coates, Mm, Colquhoun, Sm, Cooper, C, Cortinovis, M, Crump, Ja, Gastroenterology & Hepatology, Health Services Management & Organisation (HSMO), Public Health, Psychiatry, Vos, Theo, Allen, Christine, Arora, Megha, Barber, Ryan M, Bhutta, Zulfiqar A, Brown, Alexandria, Carter, Austin, Casey, Daniel C, Charlson, Fiona J, Chen, Alan Z, Coggeshall, Megan, Cornaby, Leslie, Dandona, Lalit, Dicker, Daniel J, Dilegge, Tina, Erskine, Holly E, Ferrari, Alize J, Fitzmaurice, Christina, Fleming, Tom, Forouzanfar, Mohammad H, Fullman, Nancy, Gething, Peter W, Goldberg, Ellen M, Graetz, Nichola, Haagsma, Juanita A, Johnson, Catherine O, Kassebaum, Nicholas J, Kawashima, Toana, Kemmer, Laura, Khalil, Ibrahim A, Kinfu, Yohanne, Kyu, Hmwe H, Leung, Janni, Liang, Xiaofeng, Lim, Stephen S, Lopez, Alan D, Lozano, Rafael, Marczak, Laurie, Mensah, George A, Mokdad, Ali H, Naghavi, Mohsen, Nguyen, Grant, Nsoesie, Elaine, Olsen, Helen, Pigott, David M, Pinho, Christine, Rankin, Zane, Reinig, Nikola, Salomon, Joshua A, Sandar, Logan, Smith, Alison, Stanaway, Jeffrey, Steiner, Caitlyn, Teeple, Stephanie, Thomas, Bernadette A, Troeger, Christopher, Wagner, Joseph A, Wang, Haidong, Wanga, Valentine, Whiteford, Harvey A, Zoeckler, Leo, Abajobir, Amanuel Alemu, Abate, Kalkidan Hassen, Abbafati, Cristiana, Abbas, Kaja M, Abd-Allah, Foad, Abraham, Biju, Abubakar, Ibrahim, Abu-Raddad, Laith J, Abu-Rmeileh, Niveen M E, Ackerman, Ilana N, Adebiyi, Akindele Olupelumi, Ademi, Zanfina, Adou, Arsène Kouablan, Afanvi, Kossivi Agbelenko, Agardh, Emilie Elisabet, Agarwal, Arnav, Kiadaliri, Aliasghar Ahmad, Ahmadieh, Hamid, Ajala, Oluremi N, Akinyemi, Rufus Olusola, Akseer, Nadia, Al-Aly, Ziyad, Alam, Khurshid, Alam, Noore K M, Aldhahri, Saleh Fahed, Alegretti, Miguel Angel, Alemu, Zewdie Aderaw, Alexander, Lily T, Alhabib, Samia, Ali, Raghib, Alkerwi, Ala'A, Alla, Françoi, Allebeck, Peter, Al-Raddadi, Rajaa, Alsharif, Ubai, Altirkawi, Khalid A, Alvis-Guzman, Nelson, Amare, Azmeraw T, Amberbir, Alemayehu, Amini, Heresh, Ammar, Walid, Amrock, Stephen Marc, Andersen, Hjalte H, Anderson, Gregory M, Anderson, Benjamin O, Antonio, Carl Abelardo T, Aregay, Atsede Fantahun, Ärnlöv, Johan, Artaman, Al, Asayesh, Hamid, Assadi, Reza, Atique, Suleman, Avokpaho, Euripide Frinel G Arthur, Awasthi, Ashish, Quintanilla, Beatriz Paulina Ayala, Azzopardi, Peter, Bacha, Umar, Badawi, Alaa, Balakrishnan, Kalpana, Banerjee, Amitava, Barac, Aleksandra, Barker-Collo, Suzanne L, Bärnighausen, Till, Barregard, Lar, Barrero, Lope H, Basu, Arindam, Bazargan-Hejazi, Shahrzad, Bell, Brent, Bell, Michelle L, Bennett, Derrick A, Bensenor, Isabela M, Benzian, Habib, Berhane, Adugnaw, Bernabé, Eduardo, Betsu, Balem Demtsu, Beyene, Addisu Shunu, Bhala, Neeraj, Bhatt, Samir, Biadgilign, Sibhatu, Bienhoff, Kelly, Bikbov, Bori, Biryukov, Stan, Bisanzio, Donal, Bjertness, Espen, Blore, Jed, Borschmann, Rohan, Boufous, Soufiane, Brainin, Michael, Brazinova, Alexandra, Breitborde, Nicholas J K, Brown, Jonathan, Buchbinder, Rachelle, Buckle, Geoffrey Colin, Butt, Zahid A, Calabria, Bianca, Campos-Nonato, Ismael Ricardo, Campuzano, Julio Cesar, Carabin, Hélène, Cárdenas, Rosario, Carpenter, David O, Carrero, Juan Jesu, Castañeda-Orjuela, Carlos A, Rivas, Jacqueline Castillo, Catalá-López, Ferrán, Chang, Jung-Chen, Chiang, Peggy Pei-Chia, Chibueze, Chioma Ezinne, Chisumpa, Vesper Hichilombwe, Choi, Jee-Young Jasmine, Chowdhury, Rajiv, Christensen, Hanne, Christopher, Devasahayam Jesuda, Ciobanu, Liliana G, Coates, Matthew M, Colquhoun, Samantha M, Cooper, Cyru, Cortinovis, Monica, Crump, John A, Damtew, Solomon Abrha, Dandona, Rakhi, Daoud, Farah, Dargan, Paul I, das Neves, José, Davey, Gail, Davis, Adrian C, Leo, Diego De, Degenhardt, Louisa, Gobbo, Liana C Del, Dellavalle, Robert P, Deribe, Kebede, Deribew, Amare, Derrett, Sarah, Jarlais, Don C De, Dharmaratne, Samath D, Dhillon, Preet K, Diaz-Torné, Cesar, Ding, Eric L, Driscoll, Tim R, Duan, Leilei, Dubey, Manisha, Duncan, Bruce Bartholow, Ebrahimi, Hedyeh, Ellenbogen, Richard G, Elyazar, Iqbal, Endres, Matthia, Endries, Aman Yesuf, Ermakov, Sergey Petrovich, Eshrati, Babak, Estep, Kara, Farid, Talha A, Farinha, Carla Sofia e Sa, Faro, André, Farvid, Maryam S, Farzadfar, Farshad, Feigin, Valery L, Felson, David T, Fereshtehnejad, Seyed-Mohammad, Fernandes, Jefferson G, Fernandes, Joao C, Fischer, Florian, Fitchett, Joseph R A, Foreman, Kyle, Fowkes, F Gerry R, Fox, Jordan, Franklin, Richard C, Friedman, Joseph, Frostad, Joseph, Fürst, Thoma, Futran, Neal D, Gabbe, Belinda, Ganguly, Parthasarathi, Gankpé, Fortuné Gbètoho, Gebre, Teshome, Gebrehiwot, Tsegaye Tewelde, Gebremedhin, Amanuel Tesfay, Geleijnse, Johanna M, Gessner, Bradford D, Gibney, Katherine B, Ginawi, Ibrahim Abdelmageem Mohamed, Giref, Ababi Zergaw, Giroud, Maurice, Gishu, Melkamu Dedefo, Glaser, Elizabeth, Godwin, William W, Gomez-Dantes, Hector, Gona, Philimon, Goodridge, Amador, Gopalani, Sameer Vali, Gotay, Carolyn C, Goto, Atsushi, Gouda, Hebe N, Grainger, Rebecca, Greaves, Felix, Guillemin, Franci, Guo, Yuming, Gupta, Rahul, Gupta, Rajeev, Gupta, Vipin, Gutiérrez, Reyna A, Haile, Demewoz, Hailu, Alemayehu Desalegne, Hailu, Gessessew Bugssa, Halasa, Yara A, Hamadeh, Randah Ribhi, Hamidi, Samer, Hammami, Mouhanad, Hancock, Jamie, Handal, Alexis J, Hankey, Graeme J, Hao, Yuantao, Harb, Hilda L, Harikrishnan, Sivadasanpillai, Haro, Josep Maria, Havmoeller, Rasmu, Hay, Roderick J, Heredia-Pi, Ileana Beatriz, Heydarpour, Pouria, Hoek, Hans W, Horino, Masako, Horita, Nobuyuki, Hosgood, H Dean, Hoy, Damian G, Htet, Aung Soe, Huang, Hsiang, Huang, John J, Huynh, Chantal, Iannarone, Marissa, Iburg, Kim Moesgaard, Innos, Kaire, Inoue, Manami, Iyer, Veena J, Jacobsen, Kathryn H, Jahanmehr, Nader, Jakovljevic, Mihajlo B, Javanbakht, Mehdi, Jayatilleke, Achala Upendra, Jee, Sun Ha, Jeemon, Panniyammakal, Jensen, Paul N, Jiang, Ying, Jibat, Tariku, Jimenez-Corona, Aida, Jin, Ye, Jonas, Jost B, Kabir, Zubair, Kalkonde, Yogeshwar, Kamal, Ritul, Kan, Haidong, Karch, André, Karema, Corine Kakizi, Karimkhani, Chante, Kasaeian, Amir, Kaul, Anil, Kawakami, Norito, Keiyoro, Peter Njenga, Kemp, Andrew Haddon, Keren, Andre, Kesavachandran, Chandrasekharan Nair, Khader, Yousef Saleh, Khan, Abdur Rahman, Khan, Ejaz Ahmad, Khang, Young-Ho, Khera, Sahil, Khoja, Tawfik Ahmed Muthafer, Khubchandani, Jagdish, Kieling, Christian, Kim, Pauline, Kim, Cho-il, Kim, Daniel, Kim, Yun Jin, Kissoon, Niranjan, Knibbs, Luke D, Knudsen, Ann Kristin, Kokubo, Yoshihiro, Kolte, Dhaval, Kopec, Jacek A, Kosen, Soewarta, Kotsakis, Georgios A, Koul, Parvaiz A, Koyanagi, Ai, Kravchenko, Michael, Defo, Barthelemy Kuate, Bicer, Burcu Kucuk, Kudom, Andreas A, Kuipers, Ernst J, Kumar, G Anil, Kutz, Michael, Kwan, Gene F, Lal, Aparna, Lalloo, Ratilal, Lallukka, Tea, Lam, Hilton, Lam, Jennifer O, Langan, Sinead M, Larsson, Ander, Lavados, Pablo M, Leasher, Janet L, Leigh, Jame, Leung, Ricky, Levi, Miriam, Li, Yichong, Li, Yongmei, Liang, Juan, Liu, Shiwei, Liu, Yang, Lloyd, Belinda K, Lo, Warren D, Logroscino, Giancarlo, Looker, Katharine J, Lotufo, Paulo A, Lunevicius, Raimunda, Lyons, Ronan A, Mackay, Mark T, Magdy, Mohammed, Razek, Abd El, Mahdavi, Mahdi, Majdan, Marek, Majeed, Azeem, Malekzadeh, Reza, Marcenes, Wagner, Margolis, David Joel, Martinez-Raga, Jose, Masiye, Felix, Massano, João, Mcgarvey, Stephen Theodore, Mcgrath, John J, Mckee, Martin, Mcmahon, Brian J, Meaney, Peter A, Mehari, Alem, Mejia-Rodriguez, Fabiola, Mekonnen, Alemayehu B, Melaku, Yohannes Adama, Memiah, Peter, Memish, Ziad A, Mendoza, Walter, Meretoja, Atte, Meretoja, Tuomo J, Mhimbira, Francis Apolinary, Miller, Ted R, Mills, Edward J, Mirarefin, Mojde, Mitchell, Philip B, Mock, Charles N, Mohammadi, Alireza, Mohammed, Shafiu, Monasta, Lorenzo, Hernandez, Julio Cesar Montañez, Montico, Marcella, Mooney, Meghan D, Moradi-Lakeh, Maziar, Morawska, Lidia, Mueller, Ulrich O, Mullany, Erin, Mumford, John Everett, Murdoch, Michele E, Nachega, Jean B, Nagel, Gabriele, Naheed, Aliya, Naldi, Luigi, Nangia, Vinay, Newton, John N, Ng, Marie, Ngalesoni, Frida Namnyak, Nguyen, Quyen Le, Nisar, Muhammad Imran, Pete, Patrick Martial Nkamedjie, Nolla, Joan M, Norheim, Ole F, Norman, Rosana E, Norrving, Bo, Nunes, Bruno P, Ogbo, Felix Akpojene, Oh, In-Hwan, Ohkubo, Takayoshi, Olivares, Pedro R, Olusanya, Bolajoko Olubukunola, Olusanya, Jacob Olusegun, Ortiz, Alberto, Osman, Majdi, Ota, Erika, Pa, Mahesh, Park, Eun-Kee, Parsaeian, Mahboubeh, de Azeredo Passos, Valéria Maria, Caicedo, Angel J Paternina, Patten, Scott B, Patton, George C, Pereira, David M, Perez-Padilla, Rogelio, Perico, Norberto, Pesudovs, Konrad, Petzold, Max, Phillips, Michael Robert, Piel, Frédéric B, Pillay, Julian David, Pishgar, Farhad, Plass, Dietrich, Platts-Mills, James A, Polinder, Suzanne, Pond, Constance D, Popova, Svetlana, Poulton, Richie G, Pourmalek, Farshad, Prabhakaran, Dorairaj, Prasad, Noela M, Qorbani, Mostafa, Rabiee, Rynaz H S, Radfar, Amir, Rafay, Anwar, Rahimi, Kazem, Rahimi-Movaghar, Vafa, Rahman, Mahfuzar, Rahman, Mohammad Hifz Ur, Rahman, Sajjad Ur, Rai, Rajesh Kumar, Rajsic, Sasa, Ram, Usha, Rao, Puja, Refaat, Amany H, Reitsma, Marissa B, Remuzzi, Giuseppe, Resnikoff, Serge, Reynolds, Alex, Ribeiro, Antonio L, Blancas, Maria Jesus Rio, Roba, Hirbo Shore, Rojas-Rueda, David, Ronfani, Luca, Roshandel, Gholamreza, Roth, Gregory A, Rothenbacher, Dietrich, Roy, Ambuj, Sagar, Rajesh, Sahathevan, Ramesh, Sanabria, Juan R, Sanchez-Niño, Maria Dolore, Santos, Itamar S, Santos, João Vasco, Sarmiento-Suarez, Rodrigo, Sartorius, Benn, Satpathy, Maheswar, Savic, Miloje, Sawhney, Monika, Schaub, Michael P, Schmidt, Maria Inê, Schneider, Ione J C, Schöttker, Ben, Schwebel, David C, Scott, James G, Seedat, Soraya, Sepanlou, Sadaf G, Servan-Mori, Edson E, Shackelford, Katya A, Shaheen, Amira, Shaikh, Masood Ali, Sharma, Rajesh, Sharma, Upasana, Shen, Jiabin, Shepard, Donald S, Sheth, Kevin N, Shibuya, Kenji, Shin, Min-Jeong, Shiri, Rahman, Shiue, Ivy, Shrime, Mark G, Sigfusdottir, Inga Dora, Silva, Diego Augusto Santo, Silveira, Dayane Gabriele Alve, Singh, Abhishek, Singh, Jasvinder A, Singh, Om Prakash, Singh, Prashant Kumar, Sivonda, Anna, Skirbekk, Vegard, Skogen, Jens Christoffer, Sligar, Amber, Sliwa, Karen, Soljak, Michael, Søreide, Kjetil, Soriano, Joan B, Sposato, Luciano A, Sreeramareddy, Chandrashekhar T, Stathopoulou, Vasiliki, Steel, Nichola, Stein, Dan J, Steiner, Timothy J, Steinke, Sabine, Stovner, Lar, Stroumpoulis, Konstantino, Sunguya, Bruno F, Sur, Patrick, Swaminathan, Soumya, Sykes, Bryan L, Szoeke, Cassandra E I, Tabarés-Seisdedos, Rafael, Takala, Jukka S, Tandon, Nikhil, Tanne, David, Tavakkoli, Mohammad, Taye, Bineyam, Taylor, Hugh R, Ao, Braden J Te, Tedla, Bemnet Amare, Terkawi, Abdullah Sulieman, Thomson, Alan J, Thorne-Lyman, Andrew L, Thrift, Amanda G, Thurston, George D, Tobe-Gai, Ruoyan, Tonelli, Marcello, Topor-Madry, Roman, Topouzis, Foti, Tran, Bach Xuan, Dimbuene, Zacharie Tsala, Tsilimbaris, Miltiadi, Tura, Abera Kenay, Tuzcu, Emin Murat, Tyrovolas, Stefano, Ukwaja, Kingsley N, Undurraga, Eduardo A, Uneke, Chigozie Jesse, Uthman, Olalekan A, van Gool, Coen H, Varakin, Yuri Y, Vasankari, Tommi, Venketasubramanian, Narayanaswamy, Verma, Raj Kumar, Violante, Francesco S, Vladimirov, Sergey K, Vlassov, Vasiliy Victorovich, Vollset, Stein Emil, Wagner, Gregory R, Waller, Stephen G, Wang, Linhong, Watkins, David A, Weichenthal, Scott, Weiderpass, Elisabete, Weintraub, Robert G, Werdecker, Andrea, Westerman, Ronny, White, Richard A, Williams, Hywel C, Wiysonge, Charles Shey, Wolfe, Charles D A, Won, Sungho, Woodbrook, Rachel, Wubshet, Mamo, Xavier, Deni, Xu, Gelin, Yadav, Ajit Kumar, Yan, Lijing L, Yano, Yuichiro, Yaseri, Mehdi, Ye, Pengpeng, Yebyo, Henock Gebremedhin, Yip, Paul, Yonemoto, Naohiro, Yoon, Seok-Jun, Younis, Mustafa Z, Yu, Chuanhua, Zaidi, Zoubida, Zaki, Maysaa El Sayed, Zeeb, Hajo, Zhou, Maigeng, Zodpey, Sanjay, Zuhlke, Liesl Joanna, and Murray, Christopher J L

Subjects
Medicine(all), VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Incidence, Medicine (all), Public Health, Global Health, Social Medicine and Epidemiology, Bayes Theorem, 11 Medical And Health Sciences, Articles, Department of Error, Global Health, Cost of Illne, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Cost of Illness, disability, General & Internal Medicine, Quality-Adjusted Life Year, Prevalence, Humans, Disabled Person, Disabled Persons, Quality-Adjusted Life Years, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, Human
Abstract

Background Non-fatal outcomes of disease and injury increasingly detract from the ability of the world's population to live in full health, a trend largely attributable to an epidemiological transition in many countries from causes affecting children, to non-communicable diseases (NCDs) more common in adults. For the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015), we estimated the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015. Methods We estimated incidence and prevalence by age, sex, cause, year, and geography with a wide range of updated and standardised analytical procedures. Improvements from GBD 2013 included the addition of new data sources, updates to literature reviews for 85 causes, and the identification and inclusion of additional studies published up to November, 2015, to expand the database used for estimation of non-fatal outcomes to 60 900 unique data sources. Prevalence and incidence by cause and sequelae were determined with DisMod-MR 2.1, an improved version of the DisMod-MR Bayesian meta-regression tool first developed for GBD 2010 and GBD 2013. For some causes, we used alternative modelling strategies where the complexity of the disease was not suited to DisMod-MR 2.1 or where incidence and prevalence needed to be determined from other data. For GBD 2015 we created a summary indicator that combines measures of income per capita, educational attainment, and fertility (the Socio-demographic Index [SDI]) and used it to compare observed patterns of health loss to the expected pattern for countries or locations with similar SDI scores. Findings We generated 9·3 billion estimates from the various combinations of prevalence, incidence, and YLDs for causes, sequelae, and impairments by age, sex, geography, and year. In 2015, two causes had acute incidences in excess of 1 billion: upper respiratory infections (17·2 billion, 95% uncertainty interval [UI] 15·4–19·2 billion) and diarrhoeal diseases (2·39 billion, 2·30–2·50 billion). Eight causes of chronic disease and injury each affected more than 10% of the world's population in 2015: permanent caries, tension-type headache, iron-deficiency anaemia, age-related and other hearing loss, migraine, genital herpes, refraction and accommodation disorders, and ascariasis. The impairment that affected the greatest number of people in 2015 was anaemia, with 2·36 billion (2·35–2·37 billion) individuals affected. The second and third leading impairments by number of individuals affected were hearing loss and vision loss, respectively. Between 2005 and 2015, there was little change in the leading causes of years lived with disability (YLDs) on a global basis. NCDs accounted for 18 of the leading 20 causes of age-standardised YLDs on a global scale. Where rates were decreasing, the rate of decrease for YLDs was slower than that of years of life lost (YLLs) for nearly every cause included in our analysis. For low SDI geographies, Group 1 causes typically accounted for 20–30% of total disability, largely attributable to nutritional deficiencies, malaria, neglected tropical diseases, HIV/AIDS, and tuberculosis. Lower back and neck pain was the leading global cause of disability in 2015 in most countries. The leading cause was sense organ disorders in 22 countries in Asia and Africa and one in central Latin America; diabetes in four countries in Oceania; HIV/AIDS in three southern sub-Saharan African countries; collective violence and legal intervention in two north African and Middle Eastern countries; iron-deficiency anaemia in Somalia and Venezuela; depression in Uganda; onchoceriasis in Liberia; and other neglected tropical diseases in the Democratic Republic of the Congo. Interpretation Ageing of the world's population is increasing the number of people living with sequelae of diseases and injuries. Shifts in the epidemiological profile driven by socioeconomic change also contribute to the continued increase in years lived with disability (YLDs) as well as the rate of increase in YLDs. Despite limitations imposed by gaps in data availability and the variable quality of the data available, the standardised and comprehensive approach of the GBD study provides opportunities to examine broad trends, compare those trends between countries or subnational geographies, benchmark against locations at similar stages of development, and gauge the strength or weakness of the estimates available. Funding Bill & Melinda Gates Foundation. Open Access funded by Bill & Melinda Gates FoundationUnder a Creative Commons license Attribution 4.0 International (CC BY 4.0)

Published
2016

46. Serotonin uptake and metabolism by cultured guinea pig airway smooth muscle cells

Author

Am Dodson, Kerry J. Rhoden, Gm Anderson, Dodson AM, Anderson GM, and Rhoden KJ

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Serotonin, Serotonin uptake, Monoamine oxidase, Guinea Pigs, Endogeny, Fluvoxamine, Guinea pig, Iproniazid, Internal medicine, Fluoxetine, medicine, Animals, Pharmacology (medical), Serotonin transporter, Cells, Cultured, biology, Biochemistry (medical), Muscle, Smooth, respiratory system, Trachea, Endocrinology, Clomipramine, biology.protein, Selective Serotonin Reuptake Inhibitors, medicine.drug
Abstract

Serotonin (5-hydroxytryptamine, 5-HT) is synthesized and released in the airways by pulmonary neuroendocrine cells located in the vicinity of airway smooth muscle (ASM). The aim of this study was to determine whether ASM cells contribute to the inactivation of serotonin, and investigate the role of the serotonin transporter (SERT) and monoamine oxidase (MAO) in this process. Cultured guinea pig tracheal smooth muscle cells, maintained in culture medium containing serotonin for 1–4 days, induced a decrease in 5-HT and increase in 5-HIAA in the culture medium. Changes in indole concentrations were prevented by fluvoxamine and iproniazid. Na+-sensitive [3H]-serotonin uptake into cultured ASM cells was time- and concentration-dependent (Km, 561 nM; Vmax, 1.06 pmol/mg protein/min), and inhibited by clomipramine (IC50, 13.7 nM), fluvoxamine (IC50, 0.16 μM) and fluoxetine (IC50, 0.32 μM). Western blot analysis with an anti-SERT antibody revealed a single 115 kDa immunoreactive band in ASM cell lysates. The results of this study suggest that ASM contributes to the uptake and metabolism of serotonin via SERT and MAO, respectively, and may therefore play a role in the inactivation of endogenous serotonin generated within the airway wall.

Published
2004

47. Fetal behavior and gestational serotonin reuptake inhibitor exposure: relationships between behavior, drug dosage, plasma drug level, and a measure of drug bioeffect.

Author

Salisbury AL, Anderson GM, Yang A, Stika CS, Rasmussen-Torvik LJ, Gollan JK, and Wisner KL

Abstract

Determination of the relationships between drug dosage, maternal and infant (cord blood) plasma drug concentrations, and serotonin reuptake inhibitor (SRI) bioeffect on offspring neurobehavior is crucial to assessing the effects of gestational SRI exposure. Measurement of maternal and cord blood platelet serotonin (5-HT) provides an index of inhibitory bioeffect at the 5-HT transporter and complements other measures of drug exposure. Three groups of mother-infant pairs were evaluated: (1) mothers with depression untreated with SRIs (DEP, n = 17), (2) mothers treated for depression with SRIs (DEP + SRI, n = 17), and (3) mothers who were not depressed and untreated (ND, n = 29). Fetal movement was assessed using a standardized ultrasound imaging and rating protocol. Maternal and cord blood platelet 5-HT levels were obtained from all participants. For the SRI + DEP group, maternal and infant plasma drug concentrations and an estimate of third-trimester maternal SRI drug exposure were obtained. As expected, substantially lower median platelet 5-HT levels were observed in the DEP + SRI group than in the non-exposed, combined ND and DEP groups. In non-exposed mothers and infants, platelet 5-HT levels were not affected by the presence of maternal depression. Lower maternal and infant platelet 5-HT levels were associated with more immature fetal movement quality. Although these data are limited by small sample size, the bioeffect index of in vivo platelet 5-HT transporter inhibition appears to provide a valuable approach for elucidating and possibly predicting the effects of gestational SRI exposure on fetal and perinatal neurobehavior., (© 2024. The Author(s).)

Published
2024
Full Text
View/download PDF

48. Natural clues to danger: attachment behavior in threatening situations.

Author

Chong JY, Anderson GM, and Fraley RC

Subjects
Humans, Female, Male, Adult, Young Adult, Interpersonal Relations, Adolescent, Individuality, Fear psychology, Object Attachment
Abstract

A fundamental principle of attachment theory is that threatening situations give rise to individual differences in the extent to which people seek proximity to close others. The current research examines the way in which attachment styles predict individual differences in attachment-relevant behavior during threatening events. We tested alternative theoretical perspectives concerning the association between adult attachment (specifically, attachment avoidance) and attachment behavior in the presence of natural clues to danger by observing couples ( N  = 204) when they were watching horror vs. control film excerpts. Results suggest that highly avoidant people engaged in less attachment behavior across both threatening and non-threatening situations. These findings have implications for the understanding of attachment-related processes and how working models of the self and others facilitate (or inhibit) the expression of attachment behavior.

Published
2024
Full Text
View/download PDF

50. Kynurenic acid inflammatory signaling expands in primates and impairs prefrontal cortical cognition.

Author

Yang S, Datta D, Krienen FM, Ling E, Woo E, May A, Anderson GM, Galvin VC, Gonzalez-Burgos G, Lewis DA, McCarroll SA, Arnsten AF, and Wang M

Abstract

Cognitive deficits from dorsolateral prefrontal cortex (dlPFC) dysfunction are common in neuroinflammatory disorders, including long-COVID, schizophrenia and Alzheimer's disease, and have been correlated with kynurenine inflammatory signaling. Kynurenine is further metabolized to kynurenic acid (KYNA) in brain, where it blocks NMDA and α7-nicotinic receptors (nic-α7Rs). These receptors are essential for neurotransmission in dlPFC, suggesting that KYNA may cause higher cognitive deficits in these disorders. The current study found that KYNA and its synthetic enzyme, KAT II, have greatly expanded expression in primate dlPFC in both glia and neurons. Local application of KYNA onto dlPFC neurons markedly reduced the delay-related firing needed for working memory via actions at NMDA and nic-α7Rs, while inhibition of KAT II enhanced neuronal firing in aged macaques. Systemic administration of agents that reduce KYNA production similarly improved cognitive performance in aged monkeys, suggesting a therapeutic avenue for the treatment of cognitive deficits in neuroinflammatory disorders.

Published
2024
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results