42 results on '"Latham, H"'
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2. The cost‐effectiveness of prophylaxis strategies for individuals with advanced HIV starting treatment in Africa
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Walker, Simon M., Cox, Edward, Revill, Paul, Musiime, Victor, Bwakura?Dangarembizi, Mutsa, Mallewa, Jane, Cheruiyot, Priscilla, Maitland, Kathryn, Ford, Nathan, Gibb, Diana M., Walker, A Sarah, Soares, Marta, Mugyenyi, P, Kityo, C, Musiime, V, Wavamunno, P, Nambi, E, Ocitti, P, Ndigendawani, M, Kabahenda, S, Kemigisa, M, Acen, J, Olebo, D, Mpamize, G, Amone, A, Okweny, D, Mbonye, A, Nambaziira, F, Rweyora, A, Kangah, M, Kabaswahili, V, Abach, J, Abongomera, G, Omongin, J, Aciro, I, Philliam, A, Arach, B, Ocung, E, Amone, G, Miles, P, Adong, C, Tumsuiime, C, Kidega, P, Otto, B, Apio, F, Baleeta, K, Mukuye, A, Abwola, M, Ssennono, F, Baliruno, D, Tuhirwe, S, Namisi, R, Kigongo, F, Kikyonkyo, D, Mushahara, F, Tusiime, J, Musiime, A, Nankya, A, Atwongyeire, D, Sirikye, S, Mula, S, Noowe, N, Lugemwa, A, Kasozi, M, Mwebe, S, Atwine, L, Senkindu, T, Natuhurira, T, Katemba, C, Ninsiima, E, Acaku, M, Kyomuhangi, J, Ankunda, R, Tukwasibwe, D, Ayesiga, L, Hakim, J, Nathoo, K, Bwakura?Dangarembizi, M, Reid, A, Chidziva, E, Mhute, T, Tinago, Gc, Bhiri, J, Mudzingwa, S, Phiri, M, Steamer, J, Nhema, R, Warambwa, C, Musoro, G, Mutsai, S, Nemasango, B, Moyo, C, Chitongo, S, Rashirai, K, Vhembo, S, Mlambo, B, Nkomani, S, Ndemera, B, Willard, M, Berejena, C, Musodza, Y, Matiza, P, Mudenge, B, Guti, V, Etyang, A, Agutu, C, Berkley, J, Maitland, K, Njuguna, P, Mwaringa, S, Etyang, T, Awuondo, K, Wale, S, Shangala, J, Kithunga, J, Mwarumba, S, Maitha, S Said, Mutai, R, Lewa, M Lozi, Mwambingu, G, Mwanzu, A, Kalama, C, Latham, H, Shikuku, J, Fondo, A, Njogu, A, Khadenge, C, Mwakisha, B, Siika, A, Wools?Kaloustian, K, Nyandiko, W, Cheruiyot, P, Sudoi, A, Wachira, S, Meli, B, Karoney, M, Nzioka, A, Tanui, M, Mokaya, M, Ekiru, W, Mboya, C, Mwimali, D, Mengich, C, Choge, J, Injera, W, Njenga, K, Cherutich, S, Orido, M Anyango, Lwande, G Omondi, Rutto, P, Mudogo, A, Kutto, I, Shali, A, Jaika, L, Jerotich, H, Pierre, M, Mallewa, J, Kaunda, S, Van Oosterhout, J, O'Hare, B, Heydermann, R, Gonzalez, C, Dzabala, N, Kelly, C, Denis, B, Selemani, G, Mipando, L Nyondo, Chirwa, E, Banda, P, Mvula, L, Msuku, H, Ziwoya, M, Manda, Y, Nicholas, S, Masesa, C, Mwalukomo, T, Makhaza, L, Sheha, I, Bwanali, J, Limbuni, M, Gibb, D, Thomason, M, Walker, As, Pett, S, Szubert, A, Griffiths, A, Wilkes, H, Rajapakse, C, Spyer, M, Prendergast, A, Klein, N, Rauchenberger, M, Van Looy, N, Little, E, Fairbrother, K, Cowan, F, Seeley, J, Bernays, S, Kawuma, R, Mupambireyi, Z, Kyomuhendo, F, Nakalanzi, S, Peshu, J, Ndaa, S, Chabuka, J, Mkandawire, N, Matandika, L, Kapuya, C, Weller, I, Malianga, E, Mwansambo, C, Miiro, F, Elyanu, P, Bukusi, E, Katabira, E, Mugurungi, O, Peto, T, Musoke, P, Matenga, J, Phiri, S, Lyall, H, Johnston, V, Fitzgerald, F, Post, F, Ssali, F, Arenas?Pinto, A, Turkova, A, and Bamford, A
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Cost benefit analysis ,Practice guidelines (Medicine) -- Evaluation ,HIV infection -- Diagnosis -- Care and treatment ,Cost benefit analysis ,Health - Abstract
: Introduction: Many HIV‐positive individuals in Africa have advanced disease when initiating antiretroviral therapy (ART) so have high risks of opportunistic infections and death. The REALITY trial found that an enhanced‐prophylaxis package including fluconazole reduced mortality by 27% in individuals starting ART with CD4 Methods: The REALITY trial enrolled from June 2013 to April 2015. A decision‐analytic model was developed to estimate the cost‐effectiveness of six management strategies in individuals initiating ART in the REALITY trial countries. Strategies included standard‐prophylaxis, enhanced‐prophylaxis, standard‐prophylaxis with fluconazole; and three CrAg testing strategies, the first stratifying individuals to enhanced‐prophylaxis (CrAg‐positive) or standard‐prophylaxis (CrAg‐negative), the second to enhanced‐prophylaxis (CrAg‐positive) or enhanced‐prophylaxis without fluconazole (CrAg‐negative) and the third to standard‐prophylaxis with fluconazole (CrAg‐positive) or without fluconazole (CrAg‐negative). The model estimated costs, life‐years and quality‐adjusted life‐years (QALY) over 48 weeks using three competing mortality risks: cryptococcal meningitis; tuberculosis, serious bacterial infection or other known cause; and unknown cause. Results: Enhanced‐prophylaxis was cost‐effective at cost‐effectiveness thresholds of US$300 and US$500 per QALY with an incremental cost‐effectiveness ratio (ICER) of US$157 per QALY in the CD4 Conclusions: The REALITY enhanced‐prophylaxis package in individuals with advanced HIV starting ART reduces morbidity and mortality, is practical to administer and is cost‐effective. Efforts should continue to ensure that components are accessed at lowest available prices., Introduction In low‐ and middle‐income settings, more than a third of HIV‐positive individuals starting antiretroviral therapy (ART) present with advanced disease (CD4 ≤ 200 cells/mm[sup.3]); over half of these have [...]
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- 2020
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3. Transcranial Infrared Laser Stimulation Improves Cognition in Older Bipolar Patients: Proof of Concept Study
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Erica C. Garcia-Pittman, Francisco Gonzalez-Lima, Latham H. Fink, Douglas W. Barrett, and Courtney M. O’Donnell
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Bipolar Disorder ,Prefrontal Cortex ,chemical and pharmacologic phenomena ,Stimulation ,Proof of Concept Study ,03 medical and health sciences ,Cognition ,0302 clinical medicine ,medicine ,Humans ,Bipolar disorder ,Cognitive decline ,Prefrontal cortex ,Aged ,Aged, 80 and over ,Cross-Over Studies ,business.industry ,Lasers ,Far-infrared laser ,hemic and immune systems ,medicine.disease ,030227 psychiatry ,Psychiatry and Mental health ,Brain stimulation ,Neurology (clinical) ,Geriatrics and Gerontology ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
This is the first study to examine if transcranial infrared laser stimulation (TILS) improves cognition in older euthymic bipolar patients, who exhibit greater cognitive decline than is expected for age-matched controls. TILS is a non-invasive novel form of photobiomodulation that augments prefrontal oxygenation and improves cognition in young adults by upregulating the mitochondrial respiratory enzyme cytochrome-c-oxidase. We used a crossover sham-controlled design to examine if TILS to bilateral prefrontal cortex produces beneficial effects on cognition in 5 euthymic bipolar patients (ages 60-85). We measured cognitive flexibility, verbal fluency, working memory, sustained attention and impulsivity with tasks that have been shown to differentiate between healthy older adults and older bipolar adults. We found TILS-induced improvements in cognitive performance on the tasks that measure cognitive flexibility and impulsivity, after 5 weekly sessions of TILS. We concluded that TILS appeared both safe and effective in helping alleviate the accelerated cognitive decline present in older bipolar patients.
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- 2021
4. Hydrotherapy reduces pain in short-term but not in long-term in patients with hip/knee osteoarthritis- a systematic review with meta-analyses
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Tang, T.Y.S., primary, Latham, H., additional, and Banerjee, A., additional
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- 2022
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5. Rapid-Response Impulsivity: Definitions, Measurement Issues, and Clinical Implications
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Hamilton, Kristen R., Littlefield, Andrew K., Anastasio, Noelle C., Cunningham, Kathryn A., Fink, Latham H. L., Wing, Victoria C., Mathias, Charles W., Lane, Scott D., Schütz, Christian G., Swann, Alan C., Lejuez, W. C., Clark, Luke, Moeller, Gerard F., and Potenza, Marc N.
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- 2015
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6. Transcranial Infrared Laser Stimulation Improves Cognition in Older Bipolar Patients: Proof of Concept Study.
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O'Donnell, Courtney M., Barrett, Douglas W., Fink, Latham H., Garcia-Pittman, Erica C., and Gonzalez-Lima, Francisco
- Abstract
This is the first study to examine if transcranial infrared laser stimulation (TILS) improves cognition in older euthymic bipolar patients, who exhibit greater cognitive decline than is expected for age-matched controls. TILS is a non-invasive novel form of photobiomodulation that augments prefrontal oxygenation and improves cognition in young adults by upregulating the mitochondrial respiratory enzyme cytochrome-c-oxidase. We used a crossover sham-controlled design to examine if TILS to bilateral prefrontal cortex produces beneficial effects on cognition in 5 euthymic bipolar patients (ages 60-85). We measured cognitive flexibility, verbal fluency, working memory, sustained attention and impulsivity with tasks that have been shown to differentiate between healthy older adults and older bipolar adults. We found TILS-induced improvements in cognitive performance on the tasks that measure cognitive flexibility and impulsivity, after 5 weekly sessions of TILS. We concluded that TILS appeared both safe and effective in helping alleviate the accelerated cognitive decline present in older bipolar patients. [ABSTRACT FROM AUTHOR]
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- 2022
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7. Transcranial Infrared Laser Stimulation Improves Cognition in Older Bipolar Patients: Proof of Concept Study
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O’Donnell, Courtney M., primary, Barrett, Douglas W., additional, Fink, Latham H., additional, Garcia-Pittman, Erica C., additional, and Gonzalez-Lima, Francisco, additional
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- 2021
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8. Oxford Prize Poem : Coloni ab Anglia ad Ameriœ oram missi
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Latham, H., primary
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- 2013
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9. Raltegravir-intensified initial antiretroviral therapy in advanced HIV disease in Africa: A randomised controlled trial
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Kityo, C, Szubert, AJ, Siika, A, Heyderman, R, Bwakura-Dangarembizi, M, Lugemwa, A, Mwaringa, S, Griffiths, A, Nkanya, I, Kabahenda, S, Wachira, S, Musoro, G, Rajapakse, C, Etyang, T, Abach, J, Spyer, MJ, Wavamunno, P, Nyondo-Mipando, L, Chidziva, E, Nathoo, K, Klein, N, Hakim, J, Gibb, DM, Walker, AS, Pett, SL, Mugyenyi, P, Musiime, V, Nambi, E, Ocitti, P, Ndigendawani, M, Kemigisa, M, Acen, J, Olebo, D, Mpamize, G, Amone, A, Okweny, D, Mbonye, A, Nambaziira, F, Rweyora, A, Kangah, M, Kabaswahili, V, Abongomera, G, Omongin, J, Aciro, I, Philliam, A, Arach, B, Ocung, E, Amone, G, Miles, P, Adong, C, Tumsuiime, C, Kidega, P, Otto, B, Apio, F, Baleeta, K, Mukuye, A, Abwola, M, Ssennono, F, Baliruno, D, Tuhirwe, S, Namisi, R, Kigongo, F, Kikyonkyo, D, Mushahara, F, Tusiime, J, Musiime, A, Nankya, A, Atwongyeire, D, Sirikye, S, Mula, S, Noowe, N, Kasozi, M, Mwebe, S, Atwine, L, Senkindu, T, Natuhurira, T, Katemba, C, Ninsiima, E, Acaku, M, Kyomuhangi, J, Ankunda, R, Tukwasibwe, D, Ayesiga, L, Reid, A, Mhute, T, Tinago, GC, Bhiri, J, Mudzingwa, S, Phiri, M, Steamer, J, Nhema, R, Warambwa, C, Mutsai, S, Nemasango, B, Moyo, C, Chitongo, S, Rashirai, K, Vhembo, S, Mlambo, B, Nkomani, S, Ndemera, B, Willard, M, Berejena, C, Musodza, Y, Matiza, P, Mudenge, B, Guti, V, Etyang, A, Agutu, C, Berkley, J, Maitland, K, Njuguna, P, Awuondo, K, Wale, S, Shangala, J, Kithunga, J, Mwarumba, S, Maitha, SS, Mutai, R, Lewa, ML, Mwambingu, G, Mwanzu, A, Kalama, C, Latham, H, Shikuku, J, Fondo, A, Njogu, A, Khadenge, C, Mwakisha, B, Wools-Kaloustian, K, Nyandiko, W, Cheruiyot, P, Sudoi, A, Meli, B, Karoney, M, Nzioka, A, Tanui, M, Mokaya, M, Ekiru, W, Mboya, C, Mwimali, D, Mengich, C, Choge, J, Injera, W, Njenga, K, Cherutich, S, Orido, MA, Lwande, GO, Rutto, P, Mudogo, A, Kutto, I, Shali, A, Jaika, L, Jerotich, H, Pierre, M, Mallewa, J, Kaunda, S, Van Oosterhout, J, O'Hare, B, Heydermann, R, Gonzalez, C, Dzabala, N, Kelly, C, Denis, B, Selemani, G, Mipando, LN, Chirwa, E, Banda, P, Mvula, L, Msuku, H, Ziwoya, M, Manda, Y, Nicholas, S, Masesa, C, Mwalukomo, T, Makhaza, L, Sheha, I, Bwanali, J, Limbuni, M, and DiFDMRCWellcome Trust
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Adult ,Male ,Zimbabwe ,Malawi ,Adolescent ,Anti-HIV Agents ,BIOMARKERS ,CHILDREN ,HIV Infections ,Drug Administration Schedule ,Health Services Accessibility ,IMMUNE RECONSTITUTION ,EFAVIRENZ ,Young Adult ,Medicine, General & Internal ,General & Internal Medicine ,Raltegravir Potassium ,INFECTION ,Humans ,Uganda ,Child ,11 Medical and Health Sciences ,RESTORATION ,IMMUNODEFICIENCY ,Science & Technology ,MORTALITY ,ADULTS ,SOUTH-AFRICA ,Kenya ,Anti-Retroviral Agents ,Child, Preschool ,Africa ,Disease Progression ,Female ,Life Sciences & Biomedicine ,REALITY trial team ,Follow-Up Studies - Abstract
Background In sub-Saharan Africa, individuals infected with HIV who are severely immunocompromised have high mortality (about 10%) shortly after starting antiretroviral therapy (ART). This group also has the greatest risk of morbidity and mortality associated with immune reconstitution inflammatory syndrome (IRIS), a paradoxical response to successful ART. Integrase inhibitors lead to significantly more rapid declines in HIV viral load (VL) than all other ART classes. We hypothesised that intensifying standard triple-drug ART with the integrase inhibitor, raltegravir, would reduce HIV VL faster and hence reduce early mortality, although this strategy could also risk more IRIS events. Methods and findings In a 2×2×2 factorial open-label parallel-group trial, treatment-naive adults, adolescents, and children >5 years old infected with HIV, with cluster of differentiation 4 (CD4) 0.7) and despite significantly greater VL suppression with raltegravir-intensified ART at 4 weeks (343/836 [41.0%] versus 113/841 [13.4%] with standard ART, p < 0.001) and 12 weeks (567/789 [71.9%] versus 415/803 [51.7%] with standard ART, p < 0.001). Through 48 weeks, there was no evidence of differences in mortality (aHR = 0.98 [95% CI 0.76–1.28], p = 0.91); in serious (aHR = 0.99 [0.81–1.21], p = 0.88), grade-4 (aHR = 0.88 [0.71–1.09], p = 0.29), or ART-modifying (aHR = 0.90 [0.63–1.27], p = 0.54) adverse events (the latter occurring in 59 [6.5%] participants with raltegravir-intensified ART versus 66 [7.3%] with standard ART); in events judged compatible with IRIS (occurring in 89 [9.9%] participants with raltegravir-intensified ART versus 86 [9.5%] with standard ART, p = 0.79) or in hospitalisations (aHR = 0.94 [95% CI 0.76–1.17], p = 0.59). At 12 weeks, one and two raltegravir-intensified participants had predicted intermediate-level and high-level raltegravir resistance, respectively. At 48 weeks, the nucleoside reverse transcriptase inhibitor (NRTI) mutation K219E/Q (p = 0.004) and the non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations K101E/P (p = 0.03) and P225H (p = 0.007) were less common in virus from participants with raltegravir-intensified ART, with weak evidence of less intermediate- or high-level resistance to tenofovir (p = 0.06), abacavir (p = 0.08), and rilpivirine (p = 0.07). Limitations of the study include limited clinical, radiological, and/or microbiological information for some participants, reflecting available services at the centres, and lack of baseline genotypes. Conclusions Although 12 weeks of raltegravir intensification was well tolerated and reduced HIV viraemia significantly faster than standard triple-drug ART during the time of greatest risk for early death, this strategy did not reduce mortality or clinical events in this group and is not warranted. There was no excess of IRIS-compatible events, suggesting that integrase inhibitors can be used safely as part of standard triple-drug first-line therapy in severely immunocompromised individuals. Trial registration ClinicalTrials.gov NCT01825031.
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- 2018
10. Serotonin (5-HT) 5-HT2A Receptor (5-HT2AR):5-HT2CR Imbalance in Medial Prefrontal Cortex Associates with Motor Impulsivity
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Sonja J. Stutz, Robert M. Sears, Noelle C. Anastasio, Kenner C. Rice, F. Gerard Moeller, Kathryn A. Cunningham, Latham H. L. Fink, Sarah E. Swinford-Jackson, and Ralph J. DiLeone
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Male ,Serial reaction time ,Physiology ,Cognitive Neuroscience ,Prefrontal Cortex ,Motor Activity ,Neuropsychological Tests ,Impulsivity ,Choice Behavior ,Biochemistry ,Article ,Rats, Sprague-Dawley ,Executive Function ,Piperidines ,Animals, Outbred Strains ,Receptor, Serotonin, 5-HT2C ,medicine ,Animals ,Receptor, Serotonin, 5-HT2A ,Serotonin Antagonists ,Prefrontal cortex ,5-HT receptor ,Membrane Glycoproteins ,Antagonist ,Receptors, Interleukin-1 ,Cell Biology ,General Medicine ,Fluorobenzenes ,5-HT2C receptor ,Phenotype ,Gene Knockdown Techniques ,Impulsive Behavior ,Serotonin ,medicine.symptom ,Psychology ,Neuroscience ,Synaptosomes - Abstract
A feature of multiple neuropsychiatric disorders is motor impulsivity. Recent studies have implicated serotonin (5-HT) systems in medial prefrontal cortex (mPFC) in mediating individual differences in motor impulsivity, notably the 5-HT2AR receptor (5-HT2AR) and 5-HT2CR. We investigated the hypothesis that differences in the ratio of 5-HT2AR:5-HT2CR protein expression in mPFC would predict the individual level of motor impulsivity and that the engineered loss of the 5-HT2CR would result in high motor impulsivity concomitant with elevated 5-HT2AR expression and pharmacological sensitivity to the selective 5-HT2AR antagonist M100907. High and low impulsive rats were identified in a 1-choice serial reaction time task. Native protein levels of the 5-HT2AR and the 5-HT2CR predicted the intensity of motor impulsivity and the 5-HT2AR:5-HT2CR ratio in mPFC positively correlated with levels of premature responses in individual outbred rats. The possibility that the 5-HT2AR and 5-HT2CR act in concert to control motor impulsivity is supported by the observation that high phenotypic motor impulsivity associated with a diminished mPFC synaptosomal 5-HT2AR:5-HT2CR protein:protein interaction. Knockdown of mPFC 5-HT2CR resulted in increased motor impulsivity and triggered a functional disruption of the local 5-HT2AR:5-HT2CR balance as evidenced by a compensatory upregulation of 5-HT2AR protein expression and a leftward shift in the potency of M100907 to suppress impulsive behavior. We infer that there is an interactive relationship between the mPFC 5-HT2AR and 5-HT2CR, and that a 5-HT2AR:5-HT2CR imbalance may be a functionally-relevant mechanism underlying motor impulsivity.
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- 2015
11. 37th International Symposium on Intensive Care and Emergency Medicine (part 1 of 3)
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Karavana, V., Smith, I., Kanellis, G., Sigala, I., Kinsella, T., Zakynthinos, S., Liu, L., Chen, J., Zhang, X., Liu, A., Guo, F., Liu, S., Yang, Y., Qiu, H., Grimaldi, D. G., Kaya, E., Acicbe, O., Kayaalp, I., Asar, S., Dogan, M., Eren, G., Hergunsel, O., Pavelescu, D., Grintescu, I., Mirea, L., Guanziroli, M., Gotti, M., Marino, A., Cressoni, M., Vergani, G., Chiurazzi, C., Chiumello, D., Gattinoni, L., Spano, S., Massaro, F., Moustakas, A., Johansson, S., Larsson, A., Perchiazzi, G., Zhang, X. W., Guo, F. M., Chen, J. X., Xue, M., Qiu, H. B., Yang, L., Fister, M., Knafelj, R., Suzer, M. A., Kavlak, M. E., Atalan, H. K., Gucyetmez, B., Cakar, N., Weller, D., Grootendorst, A. F., Dijkstra, A., Kuijper, T. M., Cleffken, B. I., Regli, A., De Keulenaer, B., Van Heerden, P., Hadfield, D., Hopkins, P. A., Penhaligon, B., Reid, F., Hart, N., Rafferty, G. F., Grasselli, G., Mauri, T., Lazzeri, M., Carlesso, E., Cambiaghi, B., Eronia, N., Maffezzini, E., Bronco, A., Abbruzzese, C., Rossi, N., Foti, G., Bellani, G., Pesenti, A., Bassi, G. Li, Panigada, M., Ranzani, O., Kolobow, T., Zanella, A., Berra, L., Parrini, V., Kandil, H., Salati, G., Livigni, S., Amatu, A., Girardis, M., Barbagallo, M., Moise, G., Mercurio, G., Costa, A., Vezzani, A., Lindau, S., Babel, J., Cavana, M., Torres, A., Ranzani, O. T., Umbrello, M., Taverna, M., Formenti, P., Mistraletti, G., Vetrone, F., Baisi, A., Garnero, A. G., Novotni, D. N., Arnal, J. A., Urner, M., Fan, E., Dres, M., Vorona, S., Brochard, L., Ferguson, N. D., Goligher, E. C., Leung, C., Joynt, G., Wong, W., Lee, A., Gomersall, C., Poels, S., Casaer, M., Schetz, M., Van den Berghe, G., Meyfroidt, G., Holzgraefe, B., Von Kobyletzki, L. B., Cianchi, G., Becherucci, F., Batacchi, S., Cozzolino, M., Franchi, F., Di Valvasone, S., Ferraro, M. C., Peris, A., Phiphitthanaban, H., Wacharasint, P., Wongsrichanalai, V., Lertamornpong, A., Pengpinij, O., Wattanathum, A., Oer-areemitr, N., Boddi, M., Cappellini, E., Ciapetti, M., Di Lascio, G., Bonizzoli, M., Lazzeri, C., Katsin, M. L., Hurava, M. Y., Dzyadzko, A. M., Hermann, A., Schellongowski, P., Bojic, A., Riss, K., Robak, O., Lamm, W., Sperr, W., Staudinger, T., Buoninsegni, L. Tadini, Parodo, J., Ottaviano, A., Cecci, L., Corsi, E., Ricca, V., de Garibay, A. Perez Ruiz, Ende-Schneider, B., Schreiber, C., Kreymann, B., Turani, F., Resta, M., Niro, D., Castaldi, P., Boscolo, G., Gonsales, G., Martini, S., Belli, A., Zamidei, L., Falco, M., Lamas, T., Mendes, J., Galazzi, A., Benco, B., Binda, F., Masciopinto, L., Lissoni, A., Adamini, I., Thamjamrassri, T., Watcharotayangul, J., Numthavaj, P., Kongsareepong, S., Higuera, J., Cabestrero, D., Rey, L., Narváez, G., Blandino, A., Aroca, M., Saéz, S., De Pablo, R., Mohamed, A., Sklar, M., Munshi, L., Alban, L., Turrini, C., Taccone, P., Marenghi, C., Spadaro, S., Volta, C., Alonso, D. Cabestrero, González, L. Rey, Franci, A., Stocchi, G., Cappuccini, G., Socci, F., Guetti, C., Rastrelli, P., Nestorowicz, A., Glapinski, J., Fijalkowska-Nestorowicz, A., Wosko, J., Duprez, F., Bonus, T., Cuvelier, G., Mashayekhi, S., Ollieuz, S., Reychler, G., Kuchyn, I., Bielka, K., Sergienko, A., Jones, H., Day, C., Park, S. C., Yeom, S. R., Myatra, S. N., Gupta, S., Rajnala, V., Divatia, J., Silva, J. Villalobos, Olvera, O. Aguilera, Schulte, R. Cavazos, Bermudez, M. Castañeda, Zorrilla, L. Pariente, Ferretis, H. Lopez, García, K. Trejo, Balciuniene, N., Ramsaite, J., Kriukelyte, O., Krikscionaitiene, A., Tamosuitis, T., Terragni, P., Brazzi, L., Falco, D., Pistidda, L., Magni, G., Bartoletti, L., Mascia, L., Filippini, C., Ranieri, V., Kyriakoudi, A., Rovina, N., Koltsida, O., Konstantellou, E., Kardara, M., Kostakou, E., Gavriilidis, G., Vasileiadis, I., Koulouris, N., Koutsoukou, A., Van Snippenburg, W., Kröner, A., Flim, M., Buise, M., Hemler, R., Spronk, P., Noffsinger, B., Singh, B., Hockings, L., Spina, C., Magni, F., Di Giambattista, C., Vargiolu, A., Citerio, G., Scaramuzzo, G., Waldmann, A. D., Böhm, S. H., Ragazzi, R., Volta, C. A., Heines, S. J., Strauch, U., Van de Poll, M. C., Roekaerts, P. M., Bergmans, D. C., Sosio, S., Gatti, S., Punzi, V., Asta, A., Mroczka, J., Yaroshetskiy, A. I, Rezepov, N. A., Mandel, I. A., Gelfand, B. R., Ozen, E., Karakoc, E., Ayyildiz, A., Kara, S., Ekemen, S., Yelken, B. Buyukkidan, Saasouh, W., Freeman, J., Turan, A., Hajjej, Z., Sellami, W., Bousselmi, M., Samoud, W., Gharsallah, H., Labbene, I., Ferjani, M., Vetrugno, L., Barbariol, F., Forfori, F., Regeni, I., Della Rocca, G., Jansen, D., Jonkman, A., Doorduin, J., Roesthuis, L., Van der Hoeven, J., Heunks, L., Marocco, S. Arrigoni, Bottiroli, M., Pinciroli, R., Galanti, V., Calini, A., Gagliardone, M., Fumagalli, R., Ippolito, D., Sala, V. L., Meroni, V., Elbanna, M., Nassar, Y., Abdelmohsen, A., Yahia, M., Mongodi, S., Mojoli, F., Via, G., Tavazzi, G., Fava, F., Pozzi, M., Iotti, G. A., Bouhemad, B., Ruiz-Ferron, F., Simón, J. Serrano, Gordillo-Resina, M., Chica-Saez, V., Garcia, M. Ruiz, Vela-Colmenero, R., Redondo-Orts, M., Gontijo-Coutinho, C., Ozahata, T., Nocera, P., Franci, D., Santos, T., Carvalho-Filho, M., Fochi, O., Nacoti, M., Signori, D., Bonacina, D., Bonanomi, E., Bonvecchio, E., Stella, A., Roldi, E., Orlando, A., Luperto, M., Trunfio, D., Licitra, G., Martinelli, R., Vannini, D., Giuliano, G., Näslund, E., Lindberg, L. G., Lund, I., Frithiof, R., Nichols, A., Pentakota, S., Kodali, B., Pranskunas, A., Kiudulaite, I., Simkiene, J., Damanskyte, D., Pranskuniene, Z., Arstikyte, J., Vaitkaitis, D., Pilvinis, V., Brazaitis, M., Pool, R., Haugaa, H., Botero, A., Escobar, D., Maberry, D., Tønnessen, T., Zuckerbraun, B., Pinsky, M., Gomez, H., Lyons, H., Trimmings, A., Domizi, R., Scorcella, C., Damiani, E., Pierantozzi, S., Tondi, S., Monaldi, V., Carletti, A., Zuccari, S., Adrario, E., Pelaia, P., Donati, A., Kazune, S., Grabovskis, A., Volceka, K., Rubins, U., Bol, M., Suverein, M., Delnoij, T., Driessen, R., Heines, S., Delhaas, T., Vd Poll, M., Sels, J., Jozwiak, M., Chambaz, M., Sentenac, P., Richard, C., Monnet, X., Teboul, J. L., Bitar, Z., Maadarani, O., Al Hamdan, R., Huber, W., Malbrain, M., Chew, M., Mallat, J., Tagami, T., Hundeshagen, S., Wolf, S., Mair, S., Schmid, R., Aron, J., Adlam, M., Dua, G., Mu, L., Chen, L., Yoon, J., Clermont, G., Dubrawski, A., Duhailib, Z., Al Assas, K., Shafquat, A., Salahuddin, N., Donaghy, J., Morgan, P., Valeanu, L., Stefan, M., Provenchere, S., Longrois, D., Shaw, A., Mythen, M. G., Shook, D., Hayashida, D., Munson, S. H., Sawyer, A., Mariyaselvam, M., Blunt, M., Young, P., Nakwan, N., Khwannimit, B., Checharoen, P., Berger, D., Moller, P., Bloechlinger, S., Bloch, A., Jakob, S., Takala, J., Van den Brule, J. M., Stolk, R., Vinke, E., Van Loon, L. M., Pickkers, P., Van der Hoeven, J. G., Kox, M., Hoedemaekers, C. W., Werner-Moller, P., Bertini, P., Guarracino, F., Colosimo, D., Gonnella, S., Brizzi, G., Mancino, G., Baldassarri, R., Pinsky, M. R., Amitrano, D., Goslar, T., Stajer, D., Radsel, P., De Vos, R., Dijk, N. Bussink-van, Stringari, G., Cogo, G., Devigili, A., Graziadei, M. Ceola, Bresadola, E., Lubli, P., Amella, S., Marani, F., Polati, E., Gottin, L., Colinas, L., Hernández, G., Vicho, R., Serna, M., Canabal, A., Cuena, R., Gimenez, J., Mercado, P., Depret, F., Sassi, K., Herner, A., Abded, N., Elghonemi, M., Monir, A., Nikhilesh, J., Apurv, T., Uber, A. U., Grossestreuer, A., Moskowitz, A., Patel, P., Holmberg, M. J., Donnino, M. W., Graham, C. A., Hung, K., Lo, R., Leung, L. Y., Lee, K. H., Yeung, C. Y., Chan, S. Y., Trembach, N., Zabolotskikh, I., Caldas, J., Panerai, R., Camara, L., Ferreira, G., Almeida, J., de Oliveira, G. Queiroz, Jardim, J., Bor-Seng-Shu, E., Lima, M., Nogueira, R., Jatene, F., Zeferino, S., Galas, F., Robinson, T., Hajjar, L. A., Oliveira, M., Norgueira, R., Groehs, R., Ferreira-Santos, L., Oliveira, G., Hajjar, L., Ribeiro, J., Gaiotto, F., Lisboa, L., Fukushima, J., Rizk, S., Osawa, E., Franco, R., Kalil, R., Chlabicz, M., Sobkowicz, B., Kaminski, K., Kazimierczyk, R., Musial, W., Tycińska, A., Siranovic, M., Gopcevic, A., Gavranovic, Z. G., Horvat, A. H., Krolo, H., Rode, B., Videc, L., Trifi, A., Abdellatif, S., Ismail, K. Ben, Bouattour, A., Daly, F., Nasri, R., Lakhal, S. Ben, Beurton, A., Girotto, V., Galarza, L., Guedj, T., Iliæ, M. Karaman, Sakic, L., NN, V., Stojcic, L., Alphonsine, J., Lai, C., Tapanwong, N., Chuntupama, P., Hoellthaler, J., Lahmer, T., Latham, H., Bengtson, C. D., Satterwhite, L., Stites, M., Simpson, S. Q., Skladzien, T., Cicio, M., Garlicki, J., Serednicki, W., Wordliczek, J., Vargas, P., Salazar, A., Espinoza, M., Graf, J., Kongpolprom, N., Sanguanwong, N., Jonnada, S., Gerrard, C., Jones, N., Morley, T., Thorburn, P. T., Musaeva, T., Horst, S., Lipcsey, M., Kawati, R., Pikwer, A., Rasmusson, J., Castegren, M., Shilova, A., Yafarova, A., Gilyarov, M., Stojiljkovic, D. L. Loncar, Ulici, A., Reidt, S., Lam, T., Jancik, J., Ragab, D., Taema, K., Farouk, W., Saad, M., Liu, X., Uber, A., Montissol, S., Donnino, M., Andersen, L. W., Perlikos, F., Lagiou, M., Papalois, A., Kroupis, C., Toumpoulis, I., Carter, D., Sardo, S., Landoni, G., Kongsayreepong, S., Sungsiri, R., Wongsripunetit, P., Marchio, P., Guerra-Ojeda, S., Gimeno-Raga, M., Mauricio, M. D., Valles, S. L., Aldasoro, C., Jorda, A., Aldasoro, M., Vila, J. M., Borg, U. B., Neitenbach, A. M., García, M., González, P. Guijo, Romero, M. Gracia, Orduña, P. Saludes, Cano, A. Gil, Rhodes, A., Grounds, R. M., Cecconi, M., Lee, C., Hatib, F., Jian, Z., Rinehart, J., De Los Santos, J., Canales, C., Cannesson, M., García, M. I. Monge, Scheeren, T., Chantziara, V., Vassi, A., Michaloudis, G., Sanidas, E., Golemati, S., Bateman, R. M., Mokhtar, A., Omar, W., Aziz, K. Abdel, El Azizy, H., Nielsen, D. L. Lykke, Holler, J. G., Lassen, A., Eriksson, M., Strandberg, G., Capoletto, C., Nakamura, R., Risk, S., Park, C., Dias, F., D’Arrigo, N., Fortuna, F., Redaelli, S., Zerman, L., Becker, L., Serrano, T., Cotes, L., Ramos, F., Fadel, L., Coelho, F., Mendes, C., Real, J., Pedron, B., Kuroki, M., Costa, E., and Azevedo, L.
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Critical Care and Intensive Care Medicine ,Meeting Abstracts - Published
- 2017
12. F77. Effect of Transcranial Infrared Laser Stimulation to Left Prefrontal Cortex on Verbal Cognition
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Douglas W. Barrett, Francisco Gonzalez-Lima, Revanth Poondla, and Latham H. Fink
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business.industry ,Left prefrontal cortex ,Far-infrared laser ,Medicine ,Stimulation ,Cognition ,business ,Neuroscience ,Biological Psychiatry - Published
- 2018
13. Rapid-Response Impulsivity: Definitions, Measurement Issues, and Clinical Implications
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Andrew K. Littlefield, F. Gerard Moeller, Victoria C. Wing, Carl W. Lejuez, Alan C. Swann, Luke Clark, Kathryn A. Cunningham, Scott D. Lane, Latham H. L. Fink, Noelle C. Anastasio, Kristen R. Hamilton, Marc N. Potenza, Christian G. Schütz, and Charles W. Mathias
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media_common.quotation_subject ,Mental Disorders ,Brain ,Reproducibility of Results ,Context (language use) ,Test validity ,Impulsivity ,medicine.disease ,Personality disorders ,Article ,Developmental psychology ,Psychiatry and Mental health ,Clinical Psychology ,Consistency (negotiation) ,Action (philosophy) ,Impulsive Behavior ,medicine ,Personality ,Humans ,medicine.symptom ,Psychology ,Construct (philosophy) ,human activities ,media_common ,Cognitive psychology - Abstract
Impulsivity is a multi-faceted construct that is a core feature of multiple psychiatric conditions and personality disorders. However, progress in understanding and treating impulsivity in the context of these conditions is limited by a lack of precision and consistency in its definition and assessment. Rapid-response-impulsivity (RRI) represents a tendency toward immediate action that occurs with diminished forethought and is out of context with the present demands of the environment. Experts from the International Society for Research on Impulsivity (InSRI) met to discuss and evaluate RRI-measures in terms of reliability, sensitivity, and validity with the goal of helping researchers and clinicians make informed decisions about the use and interpretation of findings from RRI-measures. Their recommendations are described in this manuscript. Commonly-used clinical and preclinical RRI-tasks are described, and considerations are provided to guide task selection. Tasks measuring two conceptually and neurobiologically distinct types of RRI, “refraining from action initiation” (RAI) and “stopping an ongoing action” (SOA) are described. RAI and SOA-tasks capture distinct aspects of RRI that may relate to distinct clinical outcomes. The InSRI group recommends that: 1) selection of RRI-measures should be informed by careful consideration of the strengths, limitations, and practical considerations of the available measures; 2) researchers use both RAI and SOA tasks in RRI studies to allow for direct comparison of RRI types and examination of their associations with clinically relevant measures; and, 3) similar considerations should be made for human and non-human studies in an effort to harmonize and integrate pre-clinical and clinical research.
- Published
- 2015
14. 5-HT2C receptor desensitization moderates anxiety in 5-HTT deficient mice: from behavioral to cellular evidence
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Rafael Maldonado, Kathryn A. Cunningham, Latham H. L. Fink, Caroline Chevarin, José Manuel Trigo, Laurence Lanfumey, Vincent Martin, Raymond Mongeau, Cédric B. P. Martin, and M. Hamon
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Agonist ,Male ,medicine.medical_specialty ,Antidepressant drugs ,medicine.drug_class ,Serotonina ,Stimulation ,Pharmacology ,Anxiety ,Editing ,Frontal cortex ,Reuptake ,Angoixa ,Mice ,Internal medicine ,medicine ,Receptor, Serotonin, 5-HT2C ,Animals ,Pharmacology (medical) ,Interpersonal Relations ,RNA, Messenger ,C-fos mRNA ,Receptor ,Cervell -- Metabolisme ,Mice, Knockout ,Serotonin Plasma Membrane Transport Proteins ,Analysis of Variance ,Behavior, Animal ,Brain ,Feeding Behavior ,3. Good health ,Serotonin Receptor Agonists ,5-HT2C receptor ,Mice, Inbred C57BL ,Psychiatry and Mental health ,Disease Models, Animal ,Endocrinology ,Anxiogenic ,Gene Expression Regulation ,Antidepressant ,Reuptake inhibitor ,Psychology ,Serotonin2C ,Proto-Oncogene Proteins c-fos ,Research Article - Abstract
BACKGROUND: Desensitization and blockade of 5-HT2C receptors (5-HT2CR) have long been thought to be central in the therapeutic action of antidepressant drugs. However, besides behavioral pharmacology studies, there is little in vivo data documenting antidepressant-induced 5-HT2CR desensitization in specific brain areas. METHODS: Mice lacking the 5-HT reuptake carrier (5-HTT(-/-)) were used to model the consequences of chronic 5-HT reuptake inhibition with antidepressant drugs. The effect of this mutation on 5-HT2CR was evaluated at the behavioral (social interaction, novelty-suppressed feeding, and 5-HT2CR-induced hypolocomotion tests), the neurochemical, and the cellular (RT-qPCR, mRNA editing, and c-fos-induced expression) levels. RESULTS: Although 5-HTT(-/-) mice had an anxiogenic profile in the novelty-suppressed feeding test, they displayed less 5-HT2CR-mediated anxiety in response to the agonist m-chlorophenylpiperazine in the social interaction test. In addition, 5-HT2CR-mediated inhibition of a stress-induced increase in 5-HT turnover, measured in various brain areas, was markedly reduced in 5-HTT(-/-) mutants. These indices of tolerance to 5-HT2CR stimulation were associated neither with altered levels of 5-HT2CR protein and mRNA nor with changes in pre-mRNA editing in the frontal cortex. However, basal c-fos mRNA production in cells expressing 5-HT2CR was higher in 5-HTT(-/-) mutants, suggesting an altered basal activity of these cells following sustained 5-HT reuptake carrier inactivation. Furthermore, the increased c-fos mRNA expression in 5-HT2CR-like immune-positive cortical cells observed in wild-type mice treated acutely with the 5-HT2CR agonist RO-60,0175 was absent in 5-HTT(-/-) mutants. CONCLUSIONS: Such blunted responsiveness of the 5-HT2CR system, observed at the cell signaling level, probably contributes to the moderation of the anxiety phenotype in 5-HTT(-/-) mice. This work was supported by grants from INSERM, UPMC, the European Community (FP7, “Devanx” consortium, F2-2007–201714), and ANR (Sercedit 2008–2010, contract ANR-06-Neuro-045-01). Dr CBP Martin was recipient of a fellowship from the French Ministère de la Recherche during performance of this work. Dr Trigo was supported by Fundacion Alicia Koplowitz. Dr Fink (DA07287, DA034488) and Dr Cunningham (DA024157, DA020087) were supported by the National Institute on Drug Abuse grants
- Published
- 2015
15. Individual Differences in Impulsive Action Reflect Variation in the Cortical Serotonin 5-HT2A Receptor System
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F. Gerard Moeller, Noelle C. Anastasio, Kathryn A. Cunningham, Latham H. L. Fink, Kenner C. Rice, and Robert G. Fox
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Agonist ,Male ,Ketanserin ,medicine.drug_class ,Population ,Individuality ,Prefrontal Cortex ,Impulsivity ,Tritium ,Choice Behavior ,Developmental psychology ,Rats, Sprague-Dawley ,Serotonin Agents ,Piperidines ,medicine ,Reaction Time ,Animals ,Immunoprecipitation ,Receptor, Serotonin, 5-HT2A ,Prefrontal cortex ,education ,Pharmacology ,education.field_of_study ,Rats ,Fluorobenzenes ,Psychiatry and Mental health ,Dimethoxyphenylethylamine ,Head Movements ,Impulsive Behavior ,Original Article ,Serotonin ,medicine.symptom ,Psychology ,Neuroscience ,Postsynaptic density ,medicine.drug ,Protein Binding - Abstract
Impulsivity is an important feature of multiple neuropsychiatric disorders, and individual variation in the degree of inherent impulsivity could play a role in the generation or exacerbation of problematic behaviors. Serotonin (5-HT) actions at the 5-HT2AR receptor (5-HT2AR) promote and 5-HT2AR antagonists suppress impulsive action (the inability to withhold premature responses; motor impulsivity) upon systemic administration or microinfusion directly into the medial prefrontal cortex (mPFC), a node in the corticostriatal circuit that is thought to play a role in the regulation of impulsive action. We hypothesized that the functional capacity of the 5-HT2AR, which is governed by its expression, localization, and protein/protein interactions (eg, postsynaptic density 95 (PSD95)), may drive the predisposition to inherent impulsive action. Stable high-impulsive (HI) and low-impulsive (LI) phenotypes were identified from an outbred rodent population with the 1-choice serial reaction time (1-CSRT) task. HI rats exhibited a greater head-twitch response following administration of the preferential 5-HT2AR agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) and were more sensitive to the effects of the selective 5-HT2AR antagonist M100907 to suppress impulsive action relative to LI rats. A positive correlation was observed between levels of premature responses and 5-HT2AR binding density in frontal cortex ([(3)H]-ketanserin radioligand binding). Elevated mPFC 5-HT2AR protein expression concomitant with augmented association of the 5-HT2AR with PSD95 differentiated HI from LI rats. The observed differential sensitivity of HI and LI rats to 5-HT2AR ligands and associated distinct 5-HT2AR protein profiles provide evidence that spontaneously occurring individual differences in impulsive action reflect variation in the cortical 5-HT2AR system.
- Published
- 2014
16. Functional status of the serotonin 5-HT2C receptor (5-HT2CR) drives interlocked phenotypes that precipitate relapse-like behaviors in cocaine dependence
- Author
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Robert M. Sears, Thomas A. Green, Ralph J. DiLeone, Noelle C. Anastasio, Dingge Li, Sonja J. Stutz, F. Gerard Moeller, Robert G. Fox, Ronald B. Emeson, Richard T. O’Neil, Kathryn A. Cunningham, and Latham H. L. Fink
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Serial reaction time ,Male ,Population ,Prefrontal Cortex ,Self Administration ,Impulsivity ,Cocaine dependence ,Rats, Sprague-Dawley ,Cocaine-Related Disorders ,Recurrence ,medicine ,Receptor, Serotonin, 5-HT2C ,Animals ,education ,Prefrontal cortex ,Pharmacology ,education.field_of_study ,Behavior, Animal ,medicine.disease ,Rats ,5-HT2C receptor ,Psychiatry and Mental health ,Phenotype ,Cue reactivity ,Original Article ,medicine.symptom ,Psychology ,Postsynaptic density ,Neuroscience - Abstract
Relapse vulnerability in cocaine dependence is rooted in genetic and environmental determinants, and propelled by both impulsivity and the responsivity to cocaine-linked cues ('cue reactivity'). The serotonin (5-hydroxytryptamine, 5-HT) 5-HT2C receptor (5-HT2CR) within the medial prefrontal cortex (mPFC) is uniquely poised to serve as a strategic nexus to mechanistically control these behaviors. The 5-HT2CR functional capacity is regulated by a number of factors including availability of active membrane receptor pools, the composition of the 5-HT2CR macromolecular protein complex, and editing of the 5-HT2CR pre-mRNA. The one-choice serial reaction time (1-CSRT) task was used to identify impulsive action phenotypes in an outbred rat population before cocaine self-administration and assessment of cue reactivity in the form of lever presses reinforced by the cocaine-associated discrete cue complex during forced abstinence. The 1-CSRT task reliably and reproducibly identified high impulsive (HI) and low impulsive (LI) action phenotypes; HI action predicted high cue reactivity. Lower cortical 5-HT2CR membrane protein levels concomitant with higher levels of 5-HT2CR:postsynaptic density 95 complex distinguished HI rats from LI rats. The frequency of edited 5-HT2CR mRNA variants was elevated with the prediction that the protein population in HI rats favors those isoforms linked to reduced signaling capacity. Genetic loss of the mPFC 5-HT2CR induced aggregate impulsive action/cue reactivity, suggesting that depressed cortical 5-HT2CR tone confers vulnerability to these interlocked behaviors. Thus, impulsive action and cue reactivity appear to neuromechanistically overlap in rodents, with the 5-HT2CR functional status acting as a neural rheostat to regulate, in part, the intersection between these vulnerability behaviors.
- Published
- 2013
17. Serotonin (5-HT) 5-HT2A Receptor (5-HT2AR):5-HT2CR Imbalance in Medial Prefrontal Cortex Associates with Motor Impulsivity
- Author
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Anastasio, Noelle C., primary, Stutz, Sonja J., additional, Fink, Latham H. L., additional, Swinford-Jackson, Sarah E., additional, Sears, Robert M., additional, DiLeone, Ralph J., additional, Rice, Kenner C., additional, Moeller, F. Gerard, additional, and Cunningham, Kathryn A., additional
- Published
- 2015
- Full Text
- View/download PDF
18. 5-HT2C Receptor Desensitization Moderates Anxiety in 5-HTT Deficient Mice: From Behavioral to Cellular Evidence
- Author
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Martin, Cédric BP, primary, Martin, Vincent S., additional, Trigo, José M., additional, Chevarin, Caroline, additional, Maldonado, Rafael, additional, Fink, Latham H., additional, Cunningham, Kathryn A., additional, Hamon, Michel, additional, Lanfumey, Laurence, additional, and Mongeau, Raymond, additional
- Published
- 2015
- Full Text
- View/download PDF
19. A predisposition toward inherent impulsivity is associated with elevated 5-HT2AR expression
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Fink, Latham H., primary, Anastasio, Noelle C., additional, Fox, R.G., additional, Moeller, F.G., additional, and Cunningham, K.A., additional
- Published
- 2014
- Full Text
- View/download PDF
20. A predisposition toward inherent impulsivity is associated with elevated 5-HT2AR expression
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Kathryn A. Cunningham, Latham H. L. Fink, Frederick G. Moeller, Noelle C. Anastasio, and Robert G. Fox
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Pharmacology ,medicine.medical_specialty ,Public health ,Alcohol dependence ,Toxicology ,Impulsivity ,Focus group ,Mental health ,law.invention ,Psychiatry and Mental health ,Underserved Population ,Randomized controlled trial ,law ,Intervention (counseling) ,medicine ,Pharmacology (medical) ,medicine.symptom ,Psychology ,Psychiatry - Abstract
s / Drug and Alcohol Dependence 140 (2014) e2–e85 e59 Conclusions: This presentation will focus on the process of game and intervention development including multidisciplinary team building, focus groups, manual, story and videogame development, andwill include video and screenshots from the game and describe a future randomized clinical trial. Financial support: Supported by R01HD062080. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.179 Community-based buprenorphine treatment program in Baltimore City: Reaching an underserved population M. Fingerhood1, Pia M. Mauro2, D. Agus3,2, Amina A. Chaudhry1 1 Johns Hopkins Medical Institutions, Baltimore, MD, United States 2 Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltmore, MD, United States 3 Behavioral Health Leadership Institute, Baltimore
- Published
- 2014
21. Functional Status of the Serotonin 5-HT2C Receptor (5-HT2CR) Drives Interlocked Phenotypes that Precipitate Relapse-Like Behaviors in Cocaine Dependence
- Author
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Anastasio, Noelle C, primary, Stutz, Sonja J, additional, Fox, Robert G, additional, Sears, Robert M, additional, Emeson, Ronald B, additional, DiLeone, Ralph J, additional, O'Neil, Richard T, additional, Fink, Latham H, additional, Li, Dingge, additional, Green, Thomas A, additional, Gerard Moeller, F, additional, and Cunningham, Kathryn A, additional
- Published
- 2013
- Full Text
- View/download PDF
22. Balance of plant challenges for a near-term EU demonstration power plant
- Author
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Porton, M., primary, Latham, H., additional, Vizvary, Z., additional, and Surrey, E., additional
- Published
- 2013
- Full Text
- View/download PDF
23. Temperature stress-induced bleaching of the coralline alga Corallina officinalis: a role for the enzyme bromoperoxidase
- Author
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Latham, H., primary
- Published
- 2008
- Full Text
- View/download PDF
24. Functional Status of the Serotonin 5-HT2C Receptor (5-HT2CR) Drives Interlocked Phenotypes that Precipitate Relapse-Like Behaviors in Cocaine Dependence.
- Author
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Anastasio, Noelle C, Stutz, Sonja J, Fox, Robert G, Sears, Robert M, Emeson, Ronald B, DiLeone, Ralph J, O'Neil, Richard T, Fink, Latham H, Li, Dingge, Green, Thomas A, Gerard Moeller, F, and Cunningham, Kathryn A
- Subjects
COCAINE ,SEROTONIN receptors ,DRUG addiction ,PREFRONTAL cortex ,MESSENGER RNA - Abstract
Relapse vulnerability in cocaine dependence is rooted in genetic and environmental determinants, and propelled by both impulsivity and the responsivity to cocaine-linked cues ('cue reactivity'). The serotonin (5-hydroxytryptamine, 5-HT) 5-HT
2C receptor (5-HT2C R) within the medial prefrontal cortex (mPFC) is uniquely poised to serve as a strategic nexus to mechanistically control these behaviors. The 5-HT2C R functional capacity is regulated by a number of factors including availability of active membrane receptor pools, the composition of the 5-HT2C R macromolecular protein complex, and editing of the 5-HT2C R pre-mRNA. The one-choice serial reaction time (1-CSRT) task was used to identify impulsive action phenotypes in an outbred rat population before cocaine self-administration and assessment of cue reactivity in the form of lever presses reinforced by the cocaine-associated discrete cue complex during forced abstinence. The 1-CSRT task reliably and reproducibly identified high impulsive (HI) and low impulsive (LI) action phenotypes; HI action predicted high cue reactivity. Lower cortical 5-HT2C R membrane protein levels concomitant with higher levels of 5-HT2C R:postsynaptic density 95 complex distinguished HI rats from LI rats. The frequency of edited 5-HT2C R mRNA variants was elevated with the prediction that the protein population in HI rats favors those isoforms linked to reduced signaling capacity. Genetic loss of the mPFC 5-HT2C R induced aggregate impulsive action/cue reactivity, suggesting that depressed cortical 5-HT2C R tone confers vulnerability to these interlocked behaviors. Thus, impulsive action and cue reactivity appear to neuromechanistically overlap in rodents, with the 5-HT2C R functional status acting as a neural rheostat to regulate, in part, the intersection between these vulnerability behaviors. [ABSTRACT FROM AUTHOR]- Published
- 2014
- Full Text
- View/download PDF
25. ChemInform Abstract: Effective Kinetic Resolution of Secondary Alcohols with a Planar‐ Chiral Analogue of 4‐(Dimethylamino)pyridine. Use of the Fe(C5Ph5) Group in Asymmetric Catalysis.
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RUBLE, J. C., primary, LATHAM, H. A., additional, and FU, G. C., additional
- Published
- 1997
- Full Text
- View/download PDF
26. Calcium regulation in ileal smooth muscle—II. Interaction of sodium and magnesium in calcium counterexchange
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Huddart, H., primary and Latham, H., additional
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- 1981
- Full Text
- View/download PDF
27. A survey of the Greater Dallas Crime Commission and its effect on the
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Latham, H. Lee
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- Criminal justice, Administration of -- Texas -- Dallas., Greater Dallas Crime Commission., Criminal justice system, Political influence, Financial influence
- Abstract
This thesis examines the history of the Greater Dallas Crime Commission and its effectiveness within the criminal justice system. It is a private agency established fifty (50) years ago to monitor and investigate the criminal justice system. Today, it serves as a source of funding for criminal justice agencies, provides awards and recognition forums for law enforcement and lobbies for legal revisions of the criminal code. The research is designed to examine their role within the criminal justice system. Whether current crime theories are supported by the commission is central to the thesis. There are no prior studies available of crime commissions perhaps because they are privately funded and operated by civilians. Crime commissions do exert influence, politically and financially, upon law enforcement. It is reflected often in their history. The extent of this effect is the subject of the paper. To this end, the commission's role in changing state laws, providing funds for police training, recognizing prosecutors and paying awards to informants lends credibility to their role in the criminal justice system. Their function has often changed during the fifty-year history. If there is a deficit, it may be that the commission has the capability, through its sphere of influence, of encouraging civilian actions that may conflict with law enforcement policy. Some examples of these are included in the study.
- Published
- 2001
28. Multiple binding modes with DNA of anthracene-9-carbonyl-N'-spermine probed by LD, CD, normal absorption, and molecular modelling compared with those of spermidine and spermine
- Author
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Adlam, G., Blagbrough, I. S., Taylor, S., and Latham, H. C.
- Published
- 1994
- Full Text
- View/download PDF
29. Advance planning for co-caring couples.
- Author
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Lezard R and Latham H
- Subjects
- Humans, Compassion Fatigue, Caregivers
- Abstract
This article explores joint advance planning for co-caring couples in the community, a group growing in number and need. A health crisis for one, exposes the vulnerability of the other. Lack of planning for this eventuality leaves health and social care struggling to provide an adequate safety net in a short timeframe. This inability to adequately support, can lead to harm to the couple. The authors conducted a formal reflective investigation to discover themes that impacted on their ability to meet the needs of such a couple in their care. The themes were: the need for advanced care planning in co-caring situations; capacity assessed through different lenses; using safeguarding systems appropriately to support questions of capacity; challenges when care is not accepted; and compassion fatigue. These themes were then used to develop an action plan to improve ways of working to reduce risk in these situations.
- Published
- 2023
- Full Text
- View/download PDF
30. The mental health of NHS staff during the COVID-19 pandemic: two-wave Scottish cohort study.
- Author
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De Kock JH, Ann Latham H, Cowden RG, Cullen B, Narzisi K, Jerdan S, Muñoz SA, Leslie SJ, McNamara N, Boggon A, and Humphry RW
- Abstract
Background: Health and social care workers (HSCWs) are at risk of experiencing adverse mental health outcomes (e.g. higher levels of anxiety and depression) because of the COVID-19 pandemic. This can have a detrimental effect on quality of care, the national response to the pandemic and its aftermath., Aims: A longitudinal design provided follow-up evidence on the mental health (changes in prevalence of disease over time) of NHS staff working at a remote health board in Scotland during the COVID-19 pandemic, and investigated the determinants of mental health outcomes over time., Method: A two-wave longitudinal study was conducted from July to September 2020. Participants self-reported levels of depression (Patient Health Questionnaire-9), anxiety (Generalised Anxiety Disorder-7) and mental well-being (Warwick-Edinburgh Mental Well-being Scale) at baseline and 1.5 months later., Results: The analytic sample of 169 participants, working in community (43%) and hospital (44%) settings, reported substantial levels of depression and anxiety, and low mental well-being at baseline (depression, 30.8%; anxiety, 20.1%; well-being, 31.9%). Although mental health remained mostly constant over time, the proportion of participants meeting the threshold for anxiety increased to 27.2% at follow-up. Multivariable modelling indicated that working with, and disruption because of, COVID-19 were associated with adverse mental health changes over time., Conclusions: HSCWs working in a remote area with low COVID-19 prevalence reported substantial levels of anxiety and depression, similar to those working in areas with high COVID-19 prevalence. Efforts to support HSCW mental health must remain a priority, and should minimise the adverse effects of working with, and disruption caused by, the COVID-19 pandemic., Competing Interests: None., (© The Author(s) 2022.)
- Published
- 2022
- Full Text
- View/download PDF
31. Fluid Management in Sepsis Hypotension and Septic Shock: Time to Transition the Conversation From Fluid Responsive to Fluid Refractory?
- Author
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Satterwhite L and Latham H
- Subjects
- Fluid Therapy, Humans, Hypotension etiology, Hypotension therapy, Sepsis complications, Sepsis therapy, Shock, Shock, Septic therapy
- Published
- 2020
- Full Text
- View/download PDF
32. Hydroxyurea-Induced Interstitial Pneumonitis: A Rare Clinical Entity.
- Author
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Kamal P, Imran M, Irum A, Latham H, and Magadan J 3rd
- Published
- 2017
33. Individual Differences in Impulsive Action Reflect Variation in the Cortical Serotonin 5-HT2A Receptor System.
- Author
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Fink LH, Anastasio NC, Fox RG, Rice KC, Moeller FG, and Cunningham KA
- Subjects
- Animals, Choice Behavior physiology, Dimethoxyphenylethylamine analogs & derivatives, Dimethoxyphenylethylamine pharmacology, Fluorobenzenes pharmacology, Head Movements drug effects, Immunoprecipitation, Impulsive Behavior drug effects, Ketanserin pharmacokinetics, Male, Piperidines pharmacology, Prefrontal Cortex drug effects, Protein Binding drug effects, Rats, Rats, Sprague-Dawley, Reaction Time drug effects, Serotonin Agents pharmacology, Tritium pharmacokinetics, Impulsive Behavior physiology, Individuality, Prefrontal Cortex metabolism, Receptor, Serotonin, 5-HT2A metabolism
- Abstract
Impulsivity is an important feature of multiple neuropsychiatric disorders, and individual variation in the degree of inherent impulsivity could play a role in the generation or exacerbation of problematic behaviors. Serotonin (5-HT) actions at the 5-HT2AR receptor (5-HT2AR) promote and 5-HT2AR antagonists suppress impulsive action (the inability to withhold premature responses; motor impulsivity) upon systemic administration or microinfusion directly into the medial prefrontal cortex (mPFC), a node in the corticostriatal circuit that is thought to play a role in the regulation of impulsive action. We hypothesized that the functional capacity of the 5-HT2AR, which is governed by its expression, localization, and protein/protein interactions (eg, postsynaptic density 95 (PSD95)), may drive the predisposition to inherent impulsive action. Stable high-impulsive (HI) and low-impulsive (LI) phenotypes were identified from an outbred rodent population with the 1-choice serial reaction time (1-CSRT) task. HI rats exhibited a greater head-twitch response following administration of the preferential 5-HT2AR agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) and were more sensitive to the effects of the selective 5-HT2AR antagonist M100907 to suppress impulsive action relative to LI rats. A positive correlation was observed between levels of premature responses and 5-HT2AR binding density in frontal cortex ([(3)H]-ketanserin radioligand binding). Elevated mPFC 5-HT2AR protein expression concomitant with augmented association of the 5-HT2AR with PSD95 differentiated HI from LI rats. The observed differential sensitivity of HI and LI rats to 5-HT2AR ligands and associated distinct 5-HT2AR protein profiles provide evidence that spontaneously occurring individual differences in impulsive action reflect variation in the cortical 5-HT2AR system.
- Published
- 2015
- Full Text
- View/download PDF
34. 5-HT2C receptor desensitization moderates anxiety in 5-HTT deficient mice: from behavioral to cellular evidence.
- Author
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Martin CB, Martin VS, Trigo JM, Chevarin C, Maldonado R, Fink LH, Cunningham KA, Hamon M, Lanfumey L, and Mongeau R
- Subjects
- Analysis of Variance, Animals, Behavior, Animal drug effects, Brain drug effects, Disease Models, Animal, Feeding Behavior drug effects, Gene Expression Regulation drug effects, Gene Expression Regulation genetics, Interpersonal Relations, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Proto-Oncogene Proteins c-fos genetics, Proto-Oncogene Proteins c-fos metabolism, RNA, Messenger metabolism, Receptor, Serotonin, 5-HT2C genetics, Serotonin Plasma Membrane Transport Proteins genetics, Serotonin Receptor Agonists pharmacology, Anxiety genetics, Anxiety metabolism, Anxiety pathology, Behavior, Animal physiology, Brain metabolism, Receptor, Serotonin, 5-HT2C metabolism, Serotonin Plasma Membrane Transport Proteins deficiency
- Abstract
Background: Desensitization and blockade of 5-HT2C receptors (5-HT2CR) have long been thought to be central in the therapeutic action of antidepressant drugs. However, besides behavioral pharmacology studies, there is little in vivo data documenting antidepressant-induced 5-HT2CR desensitization in specific brain areas., Methods: Mice lacking the 5-HT reuptake carrier (5-HTT(-/-)) were used to model the consequences of chronic 5-HT reuptake inhibition with antidepressant drugs. The effect of this mutation on 5-HT2CR was evaluated at the behavioral (social interaction, novelty-suppressed feeding, and 5-HT2CR-induced hypolocomotion tests), the neurochemical, and the cellular (RT-qPCR, mRNA editing, and c-fos-induced expression) levels., Results: Although 5-HTT(-/-) mice had an anxiogenic profile in the novelty-suppressed feeding test, they displayed less 5-HT2CR-mediated anxiety in response to the agonist m-chlorophenylpiperazine in the social interaction test. In addition, 5-HT2CR-mediated inhibition of a stress-induced increase in 5-HT turnover, measured in various brain areas, was markedly reduced in 5-HTT(-/-) mutants. These indices of tolerance to 5-HT2CR stimulation were associated neither with altered levels of 5-HT2CR protein and mRNA nor with changes in pre-mRNA editing in the frontal cortex. However, basal c-fos mRNA production in cells expressing 5-HT2CR was higher in 5-HTT(-/-) mutants, suggesting an altered basal activity of these cells following sustained 5-HT reuptake carrier inactivation. Furthermore, the increased c-fos mRNA expression in 5-HT2CR-like immune-positive cortical cells observed in wild-type mice treated acutely with the 5-HT2CR agonist RO-60,0175 was absent in 5-HTT(-/-) mutants., Conclusions: Such blunted responsiveness of the 5-HT2CR system, observed at the cell signaling level, probably contributes to the moderation of the anxiety phenotype in 5-HTT(-/-) mice., (© The Author 2015. Published by Oxford University Press on behalf of CINP.)
- Published
- 2014
- Full Text
- View/download PDF
35. A regional approach to the education of nurse practitioner candidates to meet the health needs of rural Australians.
- Author
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Francis K, Boyd M, Latham H, Anderson J, Bradley A, and Manners J
- Subjects
- Australia, Health Services Needs and Demand, Nurse Practitioners education, Rural Population
- Abstract
Background: Local health services expressed interest in supporting a nurse practitioner (NP) program specifically designed for rural practice environments., Aim: To develop and deliver a generalist NP program that prepares candidates for practice in rural contexts., Methods: The Master of Clinical Nursing (Nurse Practitioner) program was designed with an understanding of the burden of disease impacting on rural Australians, application of the national health priorities, the Australian Government's refocus on preventative health care and rural health workforce shortages., Results: This program offers nurses who work in rural and remote settings an opportunity to advance their careers. Increasing the numbers of rural NPs will improve rural populations access to healthcare and potentially improve health outcomes., Conclusion: This program will equip those seeking endorsement as a NP to effectively work in rural contexts.
- Published
- 2014
- Full Text
- View/download PDF
36. Functional status of the serotonin 5-HT2C receptor (5-HT2CR) drives interlocked phenotypes that precipitate relapse-like behaviors in cocaine dependence.
- Author
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Anastasio NC, Stutz SJ, Fox RG, Sears RM, Emeson RB, DiLeone RJ, O'Neil RT, Fink LH, Li D, Green TA, Moeller FG, and Cunningham KA
- Subjects
- Animals, Behavior, Animal physiology, Cocaine-Related Disorders physiopathology, Male, Prefrontal Cortex metabolism, Prefrontal Cortex physiopathology, Rats, Rats, Sprague-Dawley, Receptor, Serotonin, 5-HT2C genetics, Recurrence, Self Administration, Cocaine-Related Disorders genetics, Cocaine-Related Disorders metabolism, Phenotype, Receptor, Serotonin, 5-HT2C deficiency, Receptor, Serotonin, 5-HT2C physiology
- Abstract
Relapse vulnerability in cocaine dependence is rooted in genetic and environmental determinants, and propelled by both impulsivity and the responsivity to cocaine-linked cues ('cue reactivity'). The serotonin (5-hydroxytryptamine, 5-HT) 5-HT2C receptor (5-HT2CR) within the medial prefrontal cortex (mPFC) is uniquely poised to serve as a strategic nexus to mechanistically control these behaviors. The 5-HT2CR functional capacity is regulated by a number of factors including availability of active membrane receptor pools, the composition of the 5-HT2CR macromolecular protein complex, and editing of the 5-HT2CR pre-mRNA. The one-choice serial reaction time (1-CSRT) task was used to identify impulsive action phenotypes in an outbred rat population before cocaine self-administration and assessment of cue reactivity in the form of lever presses reinforced by the cocaine-associated discrete cue complex during forced abstinence. The 1-CSRT task reliably and reproducibly identified high impulsive (HI) and low impulsive (LI) action phenotypes; HI action predicted high cue reactivity. Lower cortical 5-HT2CR membrane protein levels concomitant with higher levels of 5-HT2CR:postsynaptic density 95 complex distinguished HI rats from LI rats. The frequency of edited 5-HT2CR mRNA variants was elevated with the prediction that the protein population in HI rats favors those isoforms linked to reduced signaling capacity. Genetic loss of the mPFC 5-HT2CR induced aggregate impulsive action/cue reactivity, suggesting that depressed cortical 5-HT2CR tone confers vulnerability to these interlocked behaviors. Thus, impulsive action and cue reactivity appear to neuromechanistically overlap in rodents, with the 5-HT2CR functional status acting as a neural rheostat to regulate, in part, the intersection between these vulnerability behaviors.
- Published
- 2014
- Full Text
- View/download PDF
37. Closing the Gap: cultural safety in Indigenous health education.
- Author
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Rigby W, Duffy E, Manners J, Latham H, Lyons L, Crawford L, and Eldridge R
- Subjects
- Australia epidemiology, Humans, Learning, Cultural Competency, Health Education organization & administration, Native Hawaiian or Other Pacific Islander
- Abstract
The challenge for the future is to embrace a new partnership aimed at closing the gap between Indigenous and non-Indigenous Australians on life expectancy, educational achievement and employment opportunities. Significant improvements in contemporary Indigenous health care can be achieved through culturally safe health education programs for Indigenous students. However, while participation rates of Australian Indigenous students in the higher education sector are increasing, attrition rates are markedly higher than those of the general student population. This paper focuses on a unique degree program that is offered exclusively to Indigenous students in the field of mental health in the School of Nursing, Midwifery and Indigenous Health, Charles Sturt University. This qualitative exploratory study aimed to identify strategies that were especially helpful in sustaining students in the program and to identify and address barriers to the retention of students, to empower students to better prepare for the university environment and to inform academics within the course about areas that could be improved to provide a more culturally safe learning environment. The first stage of the study utilised focus group interviews with 36 Indigenous students across all three years of the program. The findings of the study addressing the issues of culturally appropriate pedagogy, curricula and cultural safety in the mental health degree program are discussed.
- Published
- 2010
- Full Text
- View/download PDF
38. Squeezing more from IT.
- Author
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Latham H
- Subjects
- Economics, Hospital organization & administration, United States, Efficiency, Organizational economics, Hospital Information Systems economics
- Published
- 2009
39. University and health service partnership: a model to deliver undergraduate nurse education in rural Australia.
- Author
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Latham H, Giffard L, and Pollard M
- Subjects
- Attitude of Health Personnel, Cooperative Behavior, Education, Distance organization & administration, Faculty, Nursing organization & administration, Focus Groups, Health Services Needs and Demand, Humans, Models, Educational, Nursing Education Research, Nursing Methodology Research, Nursing Staff, Hospital education, Nursing Staff, Hospital supply & distribution, Program Development, Program Evaluation, Students, Nursing psychology, Surveys and Questionnaires, Victoria, Education, Nursing, Baccalaureate organization & administration, Education, Professional, Retraining organization & administration, Hospitals, Rural organization & administration, Interinstitutional Relations, Nursing, Practical education, Universities organization & administration
- Abstract
A serious shortage of registered nurses at four hospitals in the Moira Shire in northern Victoria resulted in these communities forming the Moira Nurse Education Consortium to address this problem. This group approached the School of Nursing and Health Science at Charles Sturt University to deliver the Bachelor of Nursing (BN) by distance education to 25 enrolled nurses (ENs) currently employed by the participating hospitals. Development of this collaborative partnership is discussed, and findings of an evaluation study are included in the paper. Specifically the experiences of the students and the Director's of Nursing (DONs) of the participating hospitals are explored. The findings indicated that overall the participants were satisfied with the quality of the first year of the course and the functioning of the partnership. Highlights and challenges of the project are presented and directions for the future considered. This successful partnership represents innovative nursing education between rural hospitals and the School of Nursing and Health Science at Charles Sturt University. The emerging model is presented as a way to address the shortage of registered nurses in rural Australia.
- Published
- 2007
- Full Text
- View/download PDF
40. Primary fibroblasts from BRCA1 heterozygotes display an abnormal G1/S cell cycle checkpoint following UVA irradiation but show normal levels of micronuclei following oxidative stress or mitomycin C treatment.
- Author
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Shorrocks J, Tobi SE, Latham H, Peacock JH, Eeles R, Eccles D, and McMillan TJ
- Subjects
- Alkylating Agents pharmacology, Breast Neoplasms genetics, Cell Cycle drug effects, Cell Cycle genetics, Cell Cycle radiation effects, DNA Damage, Fibroblasts drug effects, Fibroblasts physiology, Genetic Predisposition to Disease, Heterozygote, Humans, Hydrogen Peroxide pharmacology, Micronuclei, Chromosome-Defective, Micronucleus Tests, Mitomycin pharmacology, Mutation, Oxidative Stress, Ultraviolet Rays, Fibroblasts radiation effects, G1 Phase genetics, Genes, BRCA1 physiology, S Phase genetics
- Abstract
Purpose: There is evidence to suggest that the breast cancer predisposing gene, BRCA1, is involved in cell cycle control and the response to damage but mouse brca1+/- heterozygotes have no distinctive phenotype. Here the response to the three forms of cellular stress was examined in primary human fibroblasts from individuals with a +/+ or +/- genotype for BRCA1., Methods and Materials: Fibroblasts from individuals carrying mutations in the BRCA1 gene were compared with those from those wild-type for BRCA1 in their response to long wavelength uv (UVA), hydrogen peroxide, and mitomycin C (MMC). Cell cycle progression and micronucleus formation (MN) were used as end points., Results: After UVA treatment there was no difference between +/- and +/+ cells in the initial fall in DNA synthetic activity (G(1) arrest) but the reentry into S-phase was restored at a faster rate in the BRCA1+/- cells after UVA exposure. Thus, for three normal (+/+) cell lines irradiated in monolayer, S-phase values averaged 15 +/- 3.7% 14 h post-UVA (1 x 10(5) J/m(2)), as compared with 35.7 +/- 1.9 (range) for two BRCA1(+/-) strains. Because a defective G(1)/S checkpoint in BRCA1 heterozygotes could lead to a greater proportion of S-phase cells with unrepaired DNA damage (strand breaks) and a resultant increase in chromosomal instability, the frequency of micronuclei induced by UVA was examined. Three normal (+/+) and three mutant (+/-) strains (two of which were used in the cell cycle experiments) produced mean micronuclei frequencies of 0.077 +/- 0.016 and 0.094 +/- 0.04/binucleate cell respectively (not statistically significant), 48 h after UVA exposure. No differences were found between BRCA1+/+ and +/- cells in MN formation after treatment with MMC or hydrogen peroxide., Conclusion: Our data suggest a defective G(1)/S checkpoint in cells from BRCA1 heterozygotes in response to UVA although this is not reflected in genomic instability as measured by micronuclei induction after oxidative stress or MMC treatment.
- Published
- 2004
- Full Text
- View/download PDF
41. Spectroscopic studies of 9-hydroxyellipticine binding to DNA.
- Author
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Ismail MA, Sanders KJ, Fennell GC, Latham HC, Wormell P, and Rodger A
- Subjects
- Animals, Antimetabolites, Antineoplastic chemistry, Antimetabolites, Antineoplastic metabolism, Binding Sites, Biopolymers chemistry, Biopolymers metabolism, Cattle, Circular Dichroism, In Vitro Techniques, Intercalating Agents chemistry, Intercalating Agents metabolism, Light, Models, Chemical, Poly dA-dT chemistry, Poly dA-dT metabolism, Polydeoxyribonucleotides chemistry, Polydeoxyribonucleotides metabolism, Scattering, Radiation, Spectrophotometry, Spectrophotometry, Ultraviolet, Thermodynamics, DNA chemistry, DNA metabolism, Ellipticines chemistry, Ellipticines metabolism
- Abstract
The binding of 9-hydroxyellipticine to calf thymus DNA, poly[d(A-T)]2, and poly[d(G-C)]2 has been studied in detail by means of CD, linear dichroism, resonance light scattering, and molecular dynamics. The transition moment polarizations of 9-hydroxyellipticine were determined in polyvinyl alcohol stretched film. Spectroscopic solution studies of the DNA/drug complex are combined with theoretical CD calculations using the final 50 ps of a series of molecular dynamics simulations as input. The spectroscopic data shows 9-hydroxyellipticine to adopt two main binding modes, one intercalative and the other a stacked binding mode involving the formation of drug oligomers in the DNA major groove. Analysis of the intercalated binding mode in poly[d(A-T)]2 suggests the 9-hydroxyellipticine hydroxyl group lies in the minor groove and hydrogen bonds to water with the pyridine ring protruding into the major groove. The stacked binding mode was examined using resonance light scattering and it was concluded that the drug was forming small oligomer stacks rather than extended aggregates. Reduced linear dichroism measurements suggested a binding geometry that precluded a minor groove binding mode where the plane of the drug makes a 45 degrees angle with the plane of the bases. Thus it was concluded that the drug stacks in the major groove. No obvious differences in the mode of binding of 9-hydroxyellipticine were observed between different DNA sequences; however, the stacked binding mode appeared to be more favorable for calf thymus DNA and poly[d(G-C)]2 than for poly[d(A-T)]2, an observation that could be explained by the slightly greater steric hindrance of the poly[d(A-T)]2 major groove. A strong concentration dependence was observed for the two binding modes where intercalation is favored at very low drug load, with stacking interactions becoming more prominent as the drug concentration is increased. Even at DNA: drug mixing ratios of 70:1 the stacked binding mode was still important for GC-rich DNAs.
- Published
- 1998
- Full Text
- View/download PDF
42. 4-Picoline-2,2':6',2"-terpyridine-platinum(II) - a potent intercalator of DNA.
- Author
-
McCoubrey A, Latham HC, Cook PR, Rodger A, and Lowe G
- Subjects
- Binding Sites, Circular Dichroism, DNA, Circular metabolism, Ethidium, Intercalating Agents chemical synthesis, Nucleic Acid Denaturation, Organoplatinum Compounds chemical synthesis, Poly dA-dT metabolism, Spectrometry, Fluorescence, DNA metabolism, Intercalating Agents metabolism, Organoplatinum Compounds metabolism
- Abstract
4-Picoloine-2,2':6',2"-terpyridine-platinum(II) is shown in a ligation assay to unwind and so intercalate into DNA. Circular dichroism is used to determine an equilibrium binding constant of approximately 2 x 10(7) M(-1) for the most stable binding mode of 4-picoline-2,2':6',2"-terpyridine-platinum(II) to poly[d(A-T)2] with a site size of about 4 base pairs, and about 1 x 10(6) M(-1) for a second binding mode with a site size of about 2 base pairs. Fluorescence spectroscopy provides further evidence for the strong equilibrium binding constant of 4-picoline-2,2':6',2"-terpyridine-platinum(II) in that it displaces ethidium bromide bound to DNA. The double positive charge on 4-picoline-2,2':6',2"-terpyridine-platinum(II), together with the intercalative binding mode is probably responsible for the large binding constant.
- Published
- 1996
- Full Text
- View/download PDF
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