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1. Ultrasonic vocalization changes and FOXP2 expression after experimental stroke.

Author

Doran, Sarah J, Trammel, Cassandra, Benashaski, Sharon E, Venna, Venugopal Reddy, and McCullough, Louise D

Subjects
*STROKE, *MEDICAL ultrasonics, *FOXP2 gene, *DEVELOPMENTAL neurobiology, *NEUROPLASTICITY, *CEREBRAL arteries, *LABORATORY mice, *GENE expression
Abstract

Speech impairments affect one in four stroke survivors. However, animal models of post-ischemic vocalization deficits are limited. Male mice vocalize at ultrasonic frequencies when exposed to an estrous female mouse. In this study we assessed vocalization patterns and quantity in male mice after cerebral ischemia. FOXP2, a gene associated with verbal dyspraxia in humans, with known roles in neurogenesis and synaptic plasticity, was also examined after injury. Using a transient middle cerebral artery occlusion (MCAO) model, we assessed correlates of vocal impairment at several time-points after stroke. Further, to identify possible lateralization of vocalization deficits induced by left and right hemispheric strokes were compared. Significant differences in vocalization quantity were observed between stroke and sham animals that persisted for a month after injury. Injury to the left hemisphere reduced early vocalizations more profoundly than those to the right hemisphere. Nuclear expression of Foxp2 was elevated early after stroke (at 6 h), but significantly decreased 24 h after injury in both the nucleus and the cytoplasm. Neuronal Foxp2 expression increased in stroke mice compared to sham animals 4 weeks after injury. This study demonstrates that quantifiable deficits in ultrasonic vocalizations (USVs) are seen after stroke. USV may be a useful tool to assess chronic behavioral recovery in murine models of stroke. [ABSTRACT FROM AUTHOR]

Published
2015
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2. Comparing Long-Acting Antipsychotic Discontinuation Rates Under Ordinary Clinical Circumstances: A Survival Analysis from an Observational, Pragmatic Study

Author

Bertolini, F., Ostuzzi, G., Pievani, M., Aguglia, A., Bartoli, F., Bortolaso, P., Callegari, C., Caroleo, M., Carra, G., Corbo, M., D'Agostino, A., De Fazio, P., Magliocco, F., Martinotti, G., Ostinelli, E. G., Piccinelli, M. P., Tedeschi, F., Barbui, C., Boschello, F., Gastaldon, C., Mazzi, M. A., Nose, M., Papola, D., Perini, G., Piccoli, A., Purgato, M., Ruggeri, M., Terlizzi, S., Turrini, G., Raffaele, G., Cavallotti, S., Chirico, M., Ferrato, F., Limosani, I., Mastromo, D., Monzani, E., Porcellana, M., Restaino, F., Annese, P. M., Bolognesi, S., Cerretini, M., De Capua, A., Debolini, S., Del Zanna, M., Fargnoli, F., Giannini, A., Luccarelli, L., Lucii, C., Pierantozzi, E., Tozzi, F., Bardicchia, F., Cardamone, G., Facchi, E., Magnani, N., Soscia, F., Biancosino, B., Zotos, S., Giacomin, M., Pompei, F., Spano, M., Zonta, F., Buzzi, A., Callegred, C., Calzolari, R., Caselli, I., Diurni, M., Giana, E., Ielmini, M., Milano, A., Poloni, N., Sani, E., Zizolfi, D., Alberini, G., Cazzamalli, S., Costantini, C., Di Caro, A., Paronelli, C., Piantanida, S., Piccinelli, M., Alessandro, P., Barbanti, S. V., D'Ippolito, C., Gozzi, M., Moretti, V., Campese, O., Di Capro, L., di Giannantonio, M., Fiori, F., Lorusso, M., Mancini, V., Viceconte, D., Calandra, C., Luca, M., Signorelli, M. S., Suraniti, F., Balzarro, B., Boncompagni, G., Caretto, V., Emiliani, R., Lupoli, P., Menchetti, M., Rossi, E., Storbini, V., Tarricone, I., Terzi, L., Boso, M., Catania, C., De Paoli, G., Risaro, P., Aspesi, F., Bava, M., Bono, A., Brambilla, G., Castagna, G., Lucchi, S., Nava, R., Provenzi, M., Tabacchi, T., Tremolada, M., Verrengia, E., Barchiesi, M., Oriani, M. G., Pacetti, M., Ferro, M., Ghio, L., Beneduce, R., Laffranchini, L., Magni, L. R., Rossi, G., Tura, G. B., Addeo, L., Balletta, G., De Vivo, E., Di Benedetto, R., Parise, V. F., Carpiniello, B., Pinna, F., Pecile, D., Mattei, C., Bonavigo, T., Fabrici, E. P., Panarello, S., Peresson, G., Vitucci, C., Gardellin, F., Strizzolo, S., Cossetta, E., Fizzotti, C., Moretti, D., Di Gregorio, L., Sozzi, F., Colli, G., La Barbera, D., Laurenzi, S., Bertolini, F, Ostuzzi, G, Pievani, M, Aguglia, A, Bartoli, F, Bortolaso, P, Callegari, C, Caroleo, M, Carra, G, Corbo, M, D'Agostino, A, De Fazio, P, Magliocco, F, Martinotti, G, Ostinelli, E, Piccinelli, M, Tedeschi, F, Barbui, C, Boschello, F, Gastaldon, C, Mazzi, M, Nose, M, Papola, D, Perini, G, Piccoli, A, Purgato, M, Ruggeri, M, Terlizzi, S, Turrini, G, Raffaele, G, Cavallotti, S, Chirico, M, Ferrato, F, Limosani, I, Mastromo, D, Monzani, E, Porcellana, M, Restaino, F, Annese, P, Bolognesi, S, Cerretini, M, De Capua, A, Debolini, S, Del Zanna, M, Fargnoli, F, Giannini, A, Luccarelli, L, Lucii, C, Pierantozzi, E, Tozzi, F, Bardicchia, F, Cardamone, G, Facchi, E, Magnani, N, Soscia, F, Biancosino, B, Zotos, S, Giacomin, M, Pompei, F, Spano, M, Zonta, F, Buzzi, A, Calzolari, R, Caselli, I, Diurni, M, Giana, E, Ielmini, M, Milano, A, Poloni, N, Sani, E, Zizolfi, D, Alberini, G, Cazzamalli, S, Costantini, C, Di Caro, A, Paronelli, C, Piantanida, S, Alessandro, P, Barbanti, S, D'Ippolito, C, Gozzi, M, Moretti, V, Campese, O, Di Capro, L, di Giannantonio, M, Fiori, F, Lorusso, M, Mancini, V, Viceconte, D, Calandra, C, Luca, M, Signorelli, M, Suraniti, F, Balzarro, B, Boncompagni, G, Caretto, V, Emiliani, R, Lupoli, P, Menchetti, M, Rossi, E, Storbini, V, Tarricone, I, Terzi, L, Boso, M, Catania, C, De Paoli, G, Risaro, P, Aspesi, F, Bava, M, Bono, A, Brambilla, G, Castagna, G, Lucchi, S, Nava, R, Provenzi, M, Tabacchi, T, Tremolada, M, Verrengia, E, Barchiesi, M, Oriani, M, Pacetti, M, Ferro, M, Ghio, L, Beneduce, R, Laffranchini, L, Magni, L, Rossi, G, Tura, G, Addeo, L, Balletta, G, De Vivo, E, Di Benedetto, R, Parise, V, Carpiniello, B, Pinna, F, Pecile, D, Mattei, C, Bonavigo, T, Fabrici, E, Panarello, S, Peresson, G, Vitucci, C, Gardellin, F, Strizzolo, S, Cossetta, E, Fizzotti, C, Moretti, D, Di Gregorio, L, Sozzi, F, Colli, G, La Barbera, D, Laurenzi, S, Bertolini F., Ostuzzi G., Pievani M., Aguglia A., Bartoli F., Bortolaso P., Callegari C., Caroleo M., Carra G., Corbo M., D'Agostino A., De Fazio P., Magliocco F., Martinotti G., Ostinelli E.G., Piccinelli M.P., Tedeschi F., Barbui C., Boschello F., Gastaldon C., Mazzi M.A., Nose M., Papola D., Perini G., Piccoli A., Purgato M., Ruggeri M., Terlizzi S., Turrini G., Raffaele G., Cavallotti S., Chirico M., Ferrato F., Limosani I., Mastromo D., Monzani E., Porcellana M., Restaino F., Annese P.M., Bolognesi S., Cerretini M., De Capua A., Debolini S., Del Zanna M., Fargnoli F., Giannini A., Luccarelli L., Lucii C., Pierantozzi E., Tozzi F., Bardicchia F., Cardamone G., Facchi E., Magnani N., Soscia F., Biancosino B., Zotos S., Giacomin M., Pompei F., Spano M., Zonta F., Buzzi A., Callegred C., Calzolari R., Caselli I., Diurni M., Giana E., Ielmini M., Milano A., Poloni N., Sani E., Zizolfi D., Alberini G., Cazzamalli S., Costantini C., Di Caro A., Paronelli C., Piantanida S., Piccinelli M., Alessandro P., Barbanti S.V., D'Ippolito C., Gozzi M., Moretti V., Campese O., Di Capro L., di Giannantonio M., Fiori F., Lorusso M., Mancini V., Viceconte D., Calandra C., Luca M., Signorelli M.S., Suraniti F., Balzarro B., Boncompagni G., Caretto V., Emiliani R., Lupoli P., Menchetti M., Rossi E., Storbini V., Tarricone I., Terzi L., Boso M., Catania C., De Paoli G., Risaro P., Aspesi F., Bava M., Bono A., Brambilla G., Castagna G., Lucchi S., Nava R., Provenzi M., Tabacchi T., Tremolada M., Verrengia E., Barchiesi M., Oriani M.G., Pacetti M., Ferro M., Ghio L., Beneduce R., Laffranchini L., Magni L.R., Rossi G., Tura G.B., Addeo L., Balletta G., De Vivo E., Di Benedetto R., Parise V.F., Carpiniello B., Pinna F., Pecile D., Mattei C., Bonavigo T., Fabrici E.P., Panarello S., Peresson G., Vitucci C., Gardellin F., Strizzolo S., Cossetta E., Fizzotti C., Moretti D., Di Gregorio L., Sozzi F., Colli G., La Barbera D., and Laurenzi S.

Subjects
Male, Pediatrics, respectively), 0302 clinical medicine, Delayed-Action Preparation, Brief Psychiatric Rating Scale, Pharmacology (medical), he STAR Network ‘Depot Study’ prospectively followed 394 subjects initiating treatment with long-acting injections (LAIs) of antipsychotics under naturalistic conditions for 12 months. LAI discontinuation was frequent in everyday clinical practice in Italy, Original Research Article, Prospective Studies, Prospective cohort study, treatment, Mental Disorders, Hazard ratio, whereas more than half of participants initiating risperidone LAI and olanzapine LAI discontinued during the 12 months of follow-up (51.4 and 62.5%, Psychiatric Status Rating Scale, Middle Aged, side efects, Psychiatry and Mental health, Italy, Mental Disorder, Female, he STAR Network ‘Depot Study’ prospectively followed 394 subjects initiating treatment with long-acting injections (LAIs) of antipsychotics under naturalistic conditions for 12 months. LAI discontinuation was frequent in everyday clinical practice in Italy, occurring in almost 40% of the entire sample, side efects, participant refusal to continue LAIs and LAIs no longer being required were the most frequently reported reasons for discontinuation. Paliperidone LAI and aripiprazole LAI were the least discontinued medications (33.9 and 35.4%, respectively), whereas more than half of participants initiating risperidone LAI and olanzapine LAI discontinued during the 12 months of follow-up (51.4 and 62.5%, respectively). In multivariate analysis, being prescribed olanzapine LAI and poor medication adherence at baseline were signifcantly associated with higher discontinuation risk, Human, Antipsychotic Agents, medicine.drug, Psychopathology, Adult, medicine.medical_specialty, Discontinuation, Follow-Up Studie, Medication Adherence, 03 medical and health sciences, medicine, Humans, Paliperidone, Adverse effect, Settore MED/25 - Psichiatria, discontinuation rates, Psychiatric Status Rating Scales, respectively). In multivariate analysis, business.industry, Long-Acting Antipsychotic, long-acting injectable antipsychotics, Survival Analysis, Confidence interval, participant refusal to continue LAIs and LAIs no longer being required were the most frequently reported reasons for discontinuation. Paliperidone LAI and aripiprazole LAI were the least discontinued medications (33.9 and 35.4%, 030227 psychiatry, Prospective Studie, Antipsychotic Agent, occurring in almost 40% of the entire sample, Delayed-Action Preparations, Neurology (clinical), business, 030217 neurology & neurosurgery, being prescribed olanzapine LAI and poor medication adherence at baseline were signifcantly associated with higher discontinuation risk, Follow-Up Studies
Abstract

Background Recent guidelines suggested a wider use of long-acting injectable antipsychotics (LAI) than previously, but naturalistic data on the consequences of LAI use in terms of discontinuation rates and associated factors are still sparse, making it hard for clinicians to be informed on plausible treatment courses. Objective Our objective was to assess, under real-world clinical circumstances, LAI discontinuation rates over a period of 12 months after a first prescription, reasons for discontinuation, and associated factors. Methods The STAR Network ‘Depot Study’ was a naturalistic, multicentre, observational prospective study that enrolled subjects initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centres were assessed at baseline and at 6 and 12 months of follow-up. Psychopathology, drug attitude and treatment adherence were measured using the Brief Psychiatric Rating Scale, the Drug Attitude Inventory and the Kemp scale, respectively. Results The study followed 394 participants for 12 months. The overall discontinuation rate at 12 months was 39.3% (95% confidence interval [CI] 34.4–44.3), with paliperidone LAI being the least discontinued LAI (33.9%; 95% CI 25.3–43.5) and olanzapine LAI the most discontinued (62.5%; 95% CI 35.4–84.8). The most frequent reason for discontinuation was onset of adverse events (32.9%; 95% CI 25.6–40.9) followed by participant refusal of the medication (20.6%; 95% CI 14.6–27.9). Medication adherence at baseline was negatively associated with discontinuation risk (hazard ratio [HR] 0.853; 95% CI 0.742–0.981; p = 0.026), whereas being prescribed olanzapine LAI was associated with increased discontinuation risk compared with being prescribed paliperidone LAI (HR 2.156; 95% CI 1.003–4.634; p = 0.049). Conclusions Clinicians should be aware that LAI discontinuation is a frequent occurrence. LAI choice should be carefully discussed with the patient, taking into account individual characteristics and possible obstacles related to the practicalities of each formulation. Supplementary Information The online version contains supplementary material available at 10.1007/s40263-021-00809-w.

Published
2021

3. Developmental expression of troponin I isoforms in fetal human heart

Author

Pankaj K. Bhavsar, Magdi H. Yacoub, Gurtej K. Dhoot, Gillian Butler-Browne, Paul J.R. Barton, and D. V. E. Cumming

Subjects
Gene isoform, medicine.medical_specialty, cardiac, Blotting, Western, Molecular Sequence Data, Biophysics, Biology, respectively), Polymerase Chain Reaction, Biochemistry, Cardiac development, Structural Biology, Internal medicine, Troponin I, Gene expression, Genetics, medicine, Humans, fast skeletal and slow skeletal muscle isoforms, RNA, Messenger, Northern blot, TnI troponin I (TnIc TnIf and Tnls, Molecular Biology, Fetus, Base Sequence, Muscles, Myocardium, Embryogenesis, Nucleic Acid Hybridization, Skeletal muscle, Heart, Cell Biology, Blotting, Northern, Troponin, Endocrinology, medicine.anatomical_structure, biology.protein
Abstract

We have used antibodies specific for troponin I proteins to examine human cardiac development and have detected a transiently expressed developmental isoform. This isoform is distinct from adult cardiac troponin I (TnIc) but is indistinguishable, on the basis of electrophoretic mobility and antibody reactivity, from the isoform found in slow skeletal muscle (TnIs). Furthermore, we show that mRNA for TnIs is present in fetal. but not adult, heart. Analysis of a developmental series of fetal samples indicates that there is a transition in expression from TnIs to TnIc which occurs between 20 weeks fetal and 9 months postnatal development.

Published
1991

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