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"Reis, Fernando"
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Estrogen-sensitive medial preoptic area neurons coordinate torpor in mice
2020
Homeotherms maintain a stable internal body temperature despite changing environments. During energy deficiency, some species can cease to defend their body temperature and enter a hypothermic and hypometabolic state known as torpor. Recent advances have revealed the medial preoptic area (MPA) as a key site for the regulation of torpor in mice. The MPA is estrogen-sensitive and estrogens also have potent effects on both temperature and metabolism. Here, we demonstrate that estrogen-sensitive neurons in the MPA can coordinate hypothermia and hypometabolism in mice. Selectively activating estrogen-sensitive MPA neurons was sufficient to drive a coordinated depression of metabolic rate and body temperature similar to torpor, as measured by body temperature, physical activity, indirect calorimetry, heart rate, and brain activity. Inducing torpor with a prolonged fast revealed larger and more variable calcium transients from estrogen-sensitive MPA neurons during bouts of hypothermia. Finally, whereas selective ablation of estrogen-sensitive MPA neurons demonstrated that these neurons are required for the full expression of fasting-induced torpor in both female and male mice, their effects on thermoregulation and torpor bout initiation exhibit differences across sex. Together, these findings suggest a role for estrogen-sensitive MPA neurons in directing the thermoregulatory and metabolic responses to energy deficiency.
Torpor is a state of reduced metabolism and body temperature that conserves energy when food is scarce. Here the authors show that estrogen-sensitive neurons in the hypothalamus regulate torpor in mice, maintaining torpor in both sexes but initiating torpor and regulating core temperature differentially across sex.
Journal Article
Guidelines for Perioperative Care in Bariatric Surgery: Enhanced Recovery After Surgery (ERAS) Society Recommendations: A 2021 Update
by
O’Kane, Mary
,
Stenberg, Erik
,
dos Reis Falcão, Luiz Fernando
in
Abdominal Surgery
,
Bariatric Surgery
,
Cardiac Surgery
2022
Background
This is the second updated Enhanced Recovery After Surgery (ERAS®) Society guideline, presenting a consensus for optimal perioperative care in bariatric surgery and providing recommendations for each ERAS item within the ERAS® protocol.
Methods
A principal literature search was performed utilizing the Pubmed, EMBASE, Cochrane databases and ClinicalTrials.gov through December 2020, with particular attention paid to meta-analyses, randomized controlled trials and large prospective cohort studies. Selected studies were examined, reviewed and graded according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. After critical appraisal of these studies, the group of authors reached consensus regarding recommendations.
Results
The quality of evidence for many ERAS interventions remains relatively low in a bariatric setting and evidence-based practices may need to be extrapolated from other surgeries.
Conclusion
A comprehensive, updated evidence-based consensus was reached and is presented in this review by the ERAS® Society.
Journal Article
Sparse genetically defined neurons refine the canonical role of periaqueductal gray columnar organization
by
La-Vu, Mimi Q
,
Sethi, Ekayana
,
Bishop, Amy
in
Brain research
,
Cholecystokinin
,
Defensive behavior
2022
During threat exposure, survival depends on defensive reactions. Prior works linked large glutamatergic populations in the midbrain periaqueductal gray (PAG) to defensive freezing and flight, and established that the overarching functional organization axis of the PAG is along anatomically-defined columns. Accordingly, broad activation of the dorsolateral column induces flight, while activation of the lateral or ventrolateral (l and vl) columns induces freezing. However, the PAG contains diverse cell types that vary in neurochemistry. How these cell types contribute to defense remains unknown, indicating that targeting sparse, genetically-defined populations may reveal how the PAG generates diverse behaviors. Though prior works showed that broad excitation of the lPAG or vlPAG causes freezing, we found in mice that activation of lateral and ventrolateral PAG (l/vlPAG) cholecystokinin-expressing (CCK) cells selectively caused flight to safer regions within an environment. Furthermore, inhibition of l/vlPAG-CCK cells reduced predator avoidance without altering other defensive behaviors like freezing. Lastly, l/vlPAG-CCK activity decreased when approaching threat and increased during movement to safer locations. These results suggest CCK cells drive threat avoidance states, which are epochs during which mice increase distance from threat and perform evasive escape. Conversely, l/vlPAG pan-neuronal activation promoted freezing, and these cells were activated near threat. Thus, CCK l/vlPAG cells have opposing function and neural activation motifs compared to the broader local ensemble defined solely by columnar boundaries. In addition to the anatomical columnar architecture of the PAG, the molecular identity of PAG cells may confer an additional axis of functional organization, revealing unexplored functional heterogeneity.
Journal Article
GABAergic CA1 neurons are more stable following context changes than glutamatergic cells
by
Kao, Jonathan C.
,
Ikebara, Juliane M.
,
Sethi, Ekayana
in
631/378/1595
,
631/378/1595/1554
,
631/378/1595/3922
2022
The CA1 region of the hippocampus contains both glutamatergic pyramidal cells and GABAergic interneurons. Numerous reports have characterized glutamatergic CAMK2A cell activity, showing how these cells respond to environmental changes such as local cue rotation and context re-sizing. Additionally, the long-term stability of spatial encoding and turnover of these cells across days is also well-characterized. In contrast, these classic hippocampal experiments have never been conducted with CA1 GABAergic cells. Here, we use chronic calcium imaging of male and female mice to compare the neural activity of VGAT and CAMK2A cells during exploration of unaltered environments and also during exposure to contexts before and after rotating and changing the length of the context across multiple recording days. Intriguingly, compared to CAMK2A cells, VGAT cells showed decreased remapping induced by environmental changes, such as context rotations and contextual length resizing. However, GABAergic neurons were also less likely than glutamatergic neurons to remain active and exhibit consistent place coding across recording days. Interestingly, despite showing significant spatial remapping across days, GABAergic cells had stable speed encoding between days. Thus, compared to glutamatergic cells, spatial encoding of GABAergic cells is more stable during within-session environmental perturbations, but is less stable across days. These insights may be crucial in accurately modeling the features and constraints of hippocampal dynamics in spatial coding.
Journal Article
Control of feeding by a bottom-up midbrain-subthalamic pathway
2024
Investigative exploration and foraging leading to food consumption have vital importance, but are not well-understood. Since GABAergic inputs to the lateral and ventrolateral periaqueductal gray (l/vlPAG) control such behaviors, we dissected the role of vgat-expressing GABAergic l/vlPAG cells in exploration, foraging and hunting. Here, we show that in mice vgat l/vlPAG cells encode approach to food and consumption of both live prey and non-prey foods. The activity of these cells is necessary and sufficient for inducing food-seeking leading to subsequent consumption. Activation of vgat l/vlPAG cells produces exploratory foraging and compulsive eating without altering defensive behaviors. Moreover, l/vlPAG vgat cells are bidirectionally interconnected to several feeding, exploration and investigation nodes, including the zona incerta. Remarkably, the vgat l/vlPAG projection to the zona incerta bidirectionally controls approach towards food leading to consumption. These data indicate the PAG is not only a final downstream target of top-down exploration and foraging-related inputs, but that it also influences these behaviors through a bottom-up pathway.
Periaqueductal gray (PAG) inputs control hunting, but foraging-inducing PAG cells were unidentified. Here, authors show that in mice activity in the projection of vgat PAG cells to the zona incerta is sufficient and necessary for food-seeking.
Journal Article
Dysmenorrhea and related disorders
by
Perelli, Federica
,
Lazzeri, Lucia
,
Petraglia, Felice
in
Endometriosis
,
Genito-Urinary & Reproductive Pharmacology
,
Menstrual Abnormalities & Abnormal Uterine Bleeding
2017
Dysmenorrhea is a common symptom secondary to various gynecological disorders, but it is also represented in most women as a primary form of disease. Pain associated with dysmenorrhea is caused by hypersecretion of prostaglandins and an increased uterine contractility. The primary dysmenorrhea is quite frequent in young women and remains with a good prognosis, even though it is associated with low quality of life. The secondary forms of dysmenorrhea are associated with endometriosis and adenomyosis and may represent the key symptom. The diagnosis is suspected on the basis of the clinical history and the physical examination and can be confirmed by ultrasound, which is very useful to exclude some secondary causes of dysmenorrhea, such as endometriosis and adenomyosis. The treatment options include non-steroidal anti-inflammatory drugs alone or combined with oral contraceptives or progestins.
Journal Article
A dual-pathway architecture for stress to disrupt agency and promote habit
by
Pimenta, Jenna S.
,
Wassum, Kate M.
,
Malvaez, Melissa
in
14/10
,
631/378/1595/1396
,
631/378/1831
2025
Chronic stress can change how we learn and, thus, how we make decisions
1
,
2
,
3
,
4
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5
. Here we investigated the neuronal circuit mechanisms that enable this. Using a multifaceted systems neuroscience approach in male and female mice, we reveal a dual-pathway, amygdala–striatal neuronal circuit architecture by which a recent history of chronic stress disrupts the action–outcome learning underlying adaptive agency and promotes the formation of inflexible habits. We found that the projection from the basolateral amygdala to the dorsomedial striatum is activated by rewarding events to support the action–outcome learning needed for flexible, goal-directed decision-making. Chronic stress attenuates this to disrupt action–outcome learning and, therefore, agency. Conversely, the projection from the central amygdala to the dorsomedial striatum mediates habit formation. Following stress, this pathway is progressively recruited to learning to promote the premature formation of inflexible habits. Thus, stress exerts opposing effects on two amygdala–striatal pathways to disrupt agency and promote habit. These data provide neuronal circuit insights into how chronic stress shapes learning and decision-making, and help understanding of how stress can lead to the disrupted decision-making and pathological habits that characterize substance use disorders and mental health conditions.
Adaptive decision-making often requires an understanding of our agency in a situation; however, chronic stress can disrupt agency and promote inflexible, habitual behaviour by turning off a brain pathway needed for agency and activating one that promotes habit.
Journal Article
Nutrition in Menopausal Women: A Narrative Review
by
Spritzer, Poli Mara
,
Oppermann, Karen
,
Silva, Thais R.
in
Anti-inflammatory diet
,
antioxidants
,
blood pressure
2021
Among the various aspects of health promotion and lifestyle adaptation to the postmenopausal period, nutritional habits are essential because they concern all women, can be modified, and impact both longevity and quality of life. In this narrative review, we discuss the current evidence on the association between dietary patterns and clinical endpoints in postmenopausal women, such as body composition, bone mass, and risk markers for cardiovascular disease. Current evidence suggests that low-fat, plant-based diets are associated with beneficial effects on body composition, but further studies are needed to confirm these results in postmenopausal women. The Mediterranean diet pattern along with other healthy habits may help the primary prevention of bone, metabolic, and cardiovascular diseases in the postmenopausal period. It consists on the use of healthy foods that have anti-inflammatory and antioxidant properties, and is associated with a small but significant decrease in blood pressure, reduction of fat mass, and improvement in cholesterol levels. These effects remain to be evaluated over a longer period of time, with the assessment of hard outcomes such as bone fractures, diabetes, and coronary ischemia.
Journal Article
Immediate Reactions to Fluorescein and Indocyanine Green in Retinal Angiography: Review of Literature and Proposal for Patient’s Evaluation
by
Rebelo Gomes, Eva
,
Marques, Maria Luís
,
Falcão-Reis, Fernando
in
adverse reactions
,
Allergies
,
Allergy
2020
Contrast rapid sequence angiography with fluorescein or indocyanine green (ICG) is a diagnostic procedure commonly used in ophthalmology. Adverse reactions to fluorescein and ICG are rare and may be classified as toxic, of hypersensitivity and non-specific. The evaluation and management of a patient with an adverse reaction is a challenge for the majority of ophthalmologists, as is the assessment of risk factors that may contraindicate the procedure.
We aim to review the concepts underlying adverse reactions to fluorescein and ICG, especially those of hypersensitivity, and present a proposal or the evaluation of the patients in need to perform retinal angiography and for the treatment of immediate reactions to fluorescein and ICG.
The available literature was examined using PubMed-Medline, and using the MeSH terms \"fluorescein\", \"Indocyanine green\", \"ophthalmic dyes\", \"retinal angiography\", \"adverse reactions\", and \"allergic reaction\".
This review may help ophthalmologists to identify patients with higher risk of a hypersensitivity reaction and give them tools to recognize patients with suspected hypersensitivity that may benefit from an allergy study.
Journal Article
Dorsal periaqueductal gray ensembles represent approach and avoidance states
by
Lee, Johannes Y
,
La-Vu, Mimi Q
,
Ikebara, Juliane M
in
Activity patterns
,
Avoidance behavior
,
Behavior
2021
Animals must balance needs to approach threats for risk assessment and to avoid danger. The dorsal periaqueductal gray (dPAG) controls defensive behaviors, but it is unknown how it represents states associated with threat approach and avoidance. We identified a dPAG threatavoidance ensemble in mice that showed higher activity farther from threats such as the open arms of the elevated plus maze and a predator. These cells were also more active during threat avoidance behaviors such as escape and freezing, even though these behaviors have antagonistic motor output. Conversely, the threat approach ensemble was more active during risk assessment behaviors and near threats. Furthermore, unsupervised methods showed that avoidance/approach states were encoded with shared activity patterns across threats. Lastly, the relative number of cells in each ensemble predicted threat avoidance across mice. Thus, dPAG ensembles dynamically encode threat approach and avoidance states, providing a flexible mechanism to balance risk assessment and danger avoidance.
Journal Article