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1.
MMWR Morb Mortal Wkly Rep ; 72(3): 49-54, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36656786

RESUMO

Influenza seasons typically begin in October and peak between December and February (1); however, the 2022-23 influenza season in Tennessee began in late September and was characterized by high pediatric hospitalization rates during November. This report describes a field investigation conducted in Tennessee during November 2022, following reports of increasing influenza hospitalizations. Data from surveillance networks, patient surveys, and whole genome sequencing of influenza virus specimens were analyzed to assess influenza activity and secondary illness risk. Influenza activity increased earlier than usual among all age groups, and rates of influenza-associated hospitalization among children were high in November, reaching 12.6 per 100,000 in children aged <5 years, comparable to peak levels typically seen in high-severity seasons. Circulating influenza viruses were genetically similar to vaccine components. Among persons who received testing for influenza at outpatient clinics, children were twice as likely to receive a positive influenza test result as were adults. Among household contacts exposed to someone with influenza, children were more than twice as likely to become ill compared with adults. As the influenza season continues, it is important for all persons, especially those at higher risk for severe disease, to protect themselves from influenza. To prevent influenza and severe influenza complications, all persons aged ≥6 months should get vaccinated, avoid contact with ill persons, and take influenza antivirals if recommended and prescribed.


Assuntos
Vacinas contra Influenza , Influenza Humana , Adulto , Criança , Humanos , Lactente , Influenza Humana/prevenção & controle , Estações do Ano , Tennessee/epidemiologia , Vírus da Influenza B/genética , Vacinação
3.
Appetite ; 127: 334-340, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29782892

RESUMO

Combination approaches for the treatment of metabolic diseases such as obesity and diabetes are becoming increasingly relevant. Co-administration of a glucagon-like peptide-1 receptor (GLP-1R) agonist with a cholecystokinin receptor-1 (CCKR1) agonist exert synergistic effects on weight loss in obese rodents. Here, we report on the effects of a novel fusion peptide (C2816) comprised of a stabilized GLP-1R agonist, AC3174, and a CCKR1-selective agonist, AC170222. C2816 was constructed such that AC3174 was linked to the N-terminus of AC170222, thus preserving the C-terminal amide of the CCK moiety. In functional in vitro assays C2816 retained full agonism at GLP-1R and CCKR1 at lower potency compared to parent molecules, whereas a previously reported fusion peptide in the opposite orientation, (pGlu-Gln)-CCK-8/exendin-4, exhibited no activity at either receptor. Acutely, in vivo, C2816 increased cFos in key central nuclei relevant to feeding behavior, and reduced food intake in wildtype (WT), but less so in GLP-1R-deficient (GLP-1RKO), mice. In sub-chronic studies in diet-induced obese (DIO) mice, C2816 exerted superior reduction in body weight compared to co-administration of AC3174 and AC170222 albeit at a higher molar dose. These data suggest that the synergistic pharmacological effects of GLP-1 and CCK pathways can be harnessed in a single therapeutic peptide.


Assuntos
Fármacos Antiobesidade/química , Colecistocinina/química , Peptídeo 1 Semelhante ao Glucagon/química , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor de Colecistocinina A/agonistas , Animais , Fármacos Antiobesidade/administração & dosagem , Fármacos Antiobesidade/farmacologia , Encéfalo/efeitos dos fármacos , Colecistocinina/administração & dosagem , Sinergismo Farmacológico , Ingestão de Alimentos/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/administração & dosagem , Receptor do Peptídeo Semelhante ao Glucagon 1/deficiência , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/tratamento farmacológico , Peptídeos/administração & dosagem , Peptídeos/química , Peptídeos/farmacologia , Ratos Sprague-Dawley , Redução de Peso
4.
Mol Metab ; 43: 101118, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33221554

RESUMO

OBJECTIVES: Combinatorial therapies are under intense investigation to develop more efficient anti-obesity drugs; however, little is known about how they act in the brain to produce enhanced anorexia and weight loss. The goal of this study was to identify the brain sites and neuronal populations engaged during the co-administration of GLP-1R and CCK1R agonists, an efficient combination therapy in obese rodents. METHODS: We measured acute and long-term feeding and body weight responses and neuronal activation patterns throughout the neuraxis and in specific neuronal subsets in response to GLP-1R and CCK1R agonists administered alone or in combination in lean and high-fat diet fed mice. We used PhosphoTRAP to obtain unbiased molecular markers for neuronal populations selectively activated by the combination of the two agonists. RESULTS: The initial anorectic response to GLP-1R and CCK1R co-agonism was mediated by a reduction in meal size, but over a few hours, a reduction in meal number accounted for the sustained feeding suppressive effects. The nucleus of the solitary tract (NTS) is one of the few brain sites where GLP-1R and CCK1R signalling interact to produce enhanced neuronal activation. None of the previously categorised NTS neuronal subpopulations relevant to feeding behaviour were implicated in this increased activation. However, we identified NTS/AP Calcrl+ neurons as treatment targets. CONCLUSIONS: Collectively, these studies indicated that circuit-level integration of GLP-1R and CCK1R co-agonism in discrete brain nuclei including the NTS produces enhanced rapid and sustained appetite suppression and weight loss.


Assuntos
Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Obesidade/tratamento farmacológico , Receptores da Colecistocinina/metabolismo , Animais , Fármacos Antiobesidade/farmacologia , Regulação do Apetite , Encéfalo/metabolismo , Dieta Hiperlipídica , Ingestão de Alimentos/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Receptor do Peptídeo Semelhante ao Glucagon 1/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Obesidade/metabolismo , Núcleo Solitário/metabolismo , Redução de Peso/efeitos dos fármacos
5.
J Appl Anim Welf Sci ; 20(2): 123-136, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28139164

RESUMO

Judgment bias tasks for nonhuman animals are promising tools to assess emotional valence as a measure of animal welfare. In view of establishing a valid judgment bias task for horses, the present study aimed to evaluate 2 versions (go/no-go and active choice) of an auditory judgment bias task for horses in terms of acquisition learning and discrimination of ambiguous cues. Five mares and 5 stallions were randomly assigned to the 2 designs and trained for 10 trials per day to acquire different operant responses to a low-frequency tone and a high-frequency tone, respectively. Following acquisition learning, horses were tested on 4 days with 3 ambiguous-tone trials interspersed between the 10 high-tone and low-tone trials. All 5 go/no-go horses but only one active-choice horse successfully learned their task, indicating that it is more difficult to train horses on an active choice task than on a go/no-go task. During testing, however, go/no-go horses did not differentiate between the 3 different ambiguous cues, thereby making the validity of the test results questionable in terms of emotional valence.


Assuntos
Comportamento Animal/fisiologia , Cognição/fisiologia , Condicionamento Operante/fisiologia , Cavalos/psicologia , Estimulação Acústica/métodos , Estimulação Acústica/veterinária , Bem-Estar do Animal , Animais , Comportamento de Escolha , Sinais (Psicologia) , Emoções , Feminino , Julgamento , Aprendizagem/fisiologia , Masculino , Distribuição Aleatória , Recompensa , Suíça
6.
Elife ; 62017 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-28532548

RESUMO

Energy dissipation through interscapular brown adipose tissue (iBAT) thermogenesis is an important contributor to adaptive energy expenditure. However, it remains unresolved how acute and chronic changes in energy availability are detected by the brain to adjust iBAT activity and maintain energy homeostasis. Here, we provide evidence that AGRP inhibitory tone to iBAT represents an energy-sparing circuit that integrates environmental food cues and internal signals of energy availability. We establish a role for the nutrient-sensing mTORC1 signaling pathway within AGRP neurons in the detection of environmental food cues and internal signals of energy availability, and in the bi-directional control of iBAT thermogenesis during nutrient deficiency and excess. Collectively, our findings provide insights into how mTORC1 signaling within AGRP neurons surveys energy availability to engage iBAT thermogenesis, and identify AGRP neurons as a neuronal substrate for the coordination of energy intake and adaptive expenditure under varying physiological and environmental contexts.


Assuntos
Proteína Relacionada com Agouti/metabolismo , Metabolismo Energético , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Neurônios/fisiologia , Tecido Adiposo/fisiologia , Animais , Camundongos , Transdução de Sinais , Termogênese
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