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1.
J Fish Biol ; 104(5): 1619-1622, 2024 May.
Article in English | MEDLINE | ID: mdl-38279785

ABSTRACT

Growth and maximum age are two key parameters that inform resilience of fish populations to exploitation. Existing information on those for greater weever inhabiting the eastern North Sea is based on the analysis of whole otoliths. Here, we present a reanalysis using sectioned otoliths. The results reveal a different growth pattern and a higher maximum age than that previously reported. The higher maximum age makes greater weever populations more vulnerable to exploitation. Such information can serve as a basis for the estimation of the growth curve that can be used for future assessment of the species.


Subject(s)
Otolithic Membrane , Animals , Otolithic Membrane/growth & development , Otolithic Membrane/chemistry , North Sea , Perciformes/growth & development
2.
Cortex ; 171: 235-246, 2024 02.
Article in English | MEDLINE | ID: mdl-38096756

ABSTRACT

Exposure to emotional body postures during perceptual decision-making tasks has been linked to transient suppression of motor reactivity, supporting the monitoring of emotionally relevant information. However, it remains unclear whether this effect occurs implicitly, i.e., when emotional information is irrelevant to the task. To investigate this issue, we used single-pulse transcranial magnetic stimulation (TMS) to assess motor excitability while healthy participants were asked to categorize pictures of body expressions as emotional or neutral (emotion recognition task) or as belonging to a male or a female actor (gender recognition task) while receiving TMS over the motor cortex at 100 and 125 ms after picture onset. Results demonstrated that motor-evoked potentials (MEPs) were reduced for emotional body postures relative to neutral postures during the emotion recognition task. Conversely, MEPs increased for emotional body postures relative to neutral postures during the gender recognition task. These findings indicate that motor inhibition, contingent upon observing emotional body postures, is selectively associated with actively monitoring emotional features. In contrast, observing emotional body postures prompts motor facilitation when task-relevant features are non-emotional. These findings contribute to embodied cognition models that link emotion perception and action tendencies.


Subject(s)
Emotions , Motor Cortex , Humans , Male , Female , Emotions/physiology , Evoked Potentials, Motor/physiology , Cognition , Motor Cortex/physiology , Transcranial Magnetic Stimulation/methods
3.
Mol Cell Biochem ; 2023 Dec 12.
Article in English | MEDLINE | ID: mdl-38082185

ABSTRACT

Anthracyclines' cardiotoxicity involves an accelerated generation of reactive oxygen species. This oxidative damage has been found to accelerate the expression of hexose-6P-dehydrogenase (H6PD), that channels glucose-6-phosphate (G6P) through the pentose phosphate pathway (PPP) confined within the endoplasmic/sarcoplasmic reticulum (SR). To verify the role of SR-PPP in the defense mechanisms activated by doxorubicin (DXR) in cardiomyocytes, we tested the effect of this drug in H6PD knockout mice (H6PD-/-). Twenty-eight wildtype (WT) and 32 H6PD-/- mice were divided into four groups to be treated with intraperitoneal administration of saline (untreated) or DXR (8 mg/Kg once a week for 3 weeks). One week thereafter, survivors underwent imaging of 18F-deoxyglucose (FDG) uptake and were sacrificed to evaluate the levels of H6PD, glucose-6P-dehydrogenase (G6PD), G6P transporter (G6PT), and malondialdehyde. The mRNA levels of SR Ca2+-ATPase 2 (Serca2) and ryanodine receptors 2 (RyR2) were evaluated and complemented with Hematoxylin/Eosin staining and transmission electron microscopy. During the treatment period, 1/14 DXR-WT and 12/18 DXR-H6PD-/- died. At microPET, DXR-H6PD-/- survivors displayed an increase in left ventricular size (p < 0.001) coupled with a decreased urinary output, suggesting a severe hemodynamic impairment. At ex vivo analysis, H6PD-/- condition was associated with an oxidative damage independent of treatment type. DXR increased H6PD expression only in WT mice, while G6PT abundance increased in both groups, mismatching a generalized decrease of G6PD levels. Switching-off SR-PPP impaired reticular accumulation of Ca2+ decelerating Serca2 expression and upregulating RyR2 mRNA level. It thus altered mitochondrial ultrastructure eventually resulting in a cardiomyocyte loss. The recognized vulnerability of SR to the anthracycline oxidative damage is counterbalanced by an acceleration of G6P flux through a PPP confined within the reticular lumen. The interplay of SR-PPP with the intracellular Ca2+ exchanges regulators in cardiomyocytes configure the reticular PPP as a potential new target for strategies aimed to decrease anthracycline toxicity.

4.
Front Psychol ; 14: 1175217, 2023.
Article in English | MEDLINE | ID: mdl-37457058

ABSTRACT

Introduction: Previous studies on embodied meaning suggest that simulations in the motor cortex play a crucial role in the processing of action sentences. However, there is little evidence that embodied meaning have functional impact beyond working memory. This study examines how the neuromodulation of the motor cortex (M1) could affect the processing of action-related language, measuring participants' performance in a long-term memory task. Method: Participants were submitted to two sessions in separate days, one with low-frequency repetitive transcranial magnetic stimulation (rTMS) and the other with sham rTMS. The pulses were delivered for 15 minutes over M1 or over V1, used as a control area. After each stimulation or sham period, the participants were asked to memorize a list of simple sentences, with a manual action verb or an attentional verb, followed in both cases by a noun referred to a manipulable object (e.g., to hang a cane vs. to observe a cane). Finally, they received the verbs as cues with instructions to recall the nouns. Results: The results showed that low frequency rTMS on M1, compared to sham stimulation, significantly improved the performance in the memory task, for both types of sentences. No change in performance was found after the rTMS stimulation of V1. Discussion: These results confirm that the perturbation on the motor system, affect the memory of manipulable object names in the context of sentences, providing further evidence of the role played by the sensorimotor system in the encoding and recall of concrete sentences of action.

5.
Cancers (Basel) ; 15(13)2023 Jul 07.
Article in English | MEDLINE | ID: mdl-37444643

ABSTRACT

BACKGROUND: Previous studies reported mitochondrial and endoplasmic reticulum redox stress in peripheral blood mononucleated cells (PBMCs) of treatment-naïve Hodgkin lymphoma (HL) patients. Here, we assessed whether this response also applies to non-HL (NHL) patients, and whether the oxidative damage is a selective feature of PBMCs or, rather, also affects tissues not directly involved in the inflammatory response. METHODS: Isolated PBMCs of 28 HL, 9 diffuse large B cell lymphoma, 8 less aggressive-NHL, and 45 controls underwent flow cytometry to evaluate redox stress and uptake of the glucose analogue 2-NBDG. This analysis was complemented with the assay of malondialdehyde (MDA) levels and enzymatic activity of glucose-6P-dehydrogenase and hexose-6P-dehydrogenase (H6PD). In all lymphoma patients, 18F-fluoro-deoxyglucose uptake was estimated in the myocardium and skeletal muscles. RESULTS: Mitochondrial reactive oxygen species generation and MDA levels were increased only in HL patients as well as H6PD activity and 2-NBDG uptake. Similarly, myocardial FDG retention was higher in HL than in other groups as opposed to a similar tracer uptake in the skeletal muscle. CONCLUSIONS: Redox stress of PBMCs is more pronounced in HL with respect to both NHL groups. This phenomenon is coherent with an increased activity of H6PD that also extends to the myocardium.

6.
Soc Cogn Affect Neurosci ; 18(1)2023 06 13.
Article in English | MEDLINE | ID: mdl-37261928

ABSTRACT

Self- and vicarious experience of physical pain induces inhibition of the motor cortex (M1). Experience of social rejections recruits the same neural network as physical pain; however, whether social pain modulates M1 corticospinal excitability remains unclear. This study examines for the first time whether social exclusion words, rather than simulated social exclusion tasks, modulate embodied sensorimotor networks during the vicarious experience of others' pain. Participants observed visual sequences of painful and functional events ending with a superimposed word with social exclusion, social inclusion or non-social meaning. Motor-evoked potentials (MEPs) to single-pulse transcranial magnetic stimulation of the left M1 were recorded at 400 or 550 ms from word onset. MEPs tended to inhibit during the observation of pain, relative to functional events. Moreover, MEPs recorded at 400 ms from word onset, during pain movies, decreased following the presentation of exclusion, relative to inclusion/neutral words. The magnitude of these two modulations marginally correlated with participants' interindividual differences in personal distress and self-esteem. These findings provide evidence of vicarious responses to others' pain in the M1 corticospinal system and enhancement of such vicarious response in the earlier phases of semantic processing of exclusion words-supporting activation of social pain-embodied representations.


Subject(s)
Motor Cortex , Pain , Humans , Transcranial Magnetic Stimulation , Evoked Potentials, Motor/physiology , Motor Cortex/physiology , Semantics
7.
J Transl Med ; 21(1): 3, 2023 01 04.
Article in English | MEDLINE | ID: mdl-36600265

ABSTRACT

BACKGROUND: Positron Emission Tomography (PET) imaging with Prostate-Specific Membrane Antigen (PSMA) and Fluorodeoxyglucose (FDG) represent promising biomarkers for risk-stratification of Prostate Cancer (PCa). We verified whether the expression of genes encoding for PSMA and enzymes regulating FDG cellular uptake are independent and additive prognosticators in PCa. METHODS: mRNA expression of genes involved in glucose metabolism and PSMA regulation obtained from primary PCa specimens were retrieved from open-source databases and analyzed using an integrative bioinformatics approach. Machine Learning (ML) techniques were used to create predictive Progression-Free Survival (PFS) models. Cellular models of primary PCa with different aggressiveness were used to compare [18F]F-PSMA-1007 and [18F]F-FDG uptake kinetics in vitro. Confocal microscopy, immunofluorescence staining, and quantification analyses were performed to assess the intracellular and cellular membrane PSMA expression. RESULTS: ML analyses identified a predictive functional network involving four glucose metabolism-related genes: ALDOB, CTH, PARP2, and SLC2A4. By contrast, FOLH1 expression (encoding for PSMA) did not provide any additive predictive value to the model. At a cellular level, the increase in proliferation rate and migratory potential by primary PCa cells was associated with enhanced FDG uptake and decreased PSMA retention (paralleled by the preferential intracellular localization). CONCLUSIONS: The overexpression of a functional network involving four glucose metabolism-related genes identifies a higher risk of disease progression since the earliest phases of PCa, in agreement with the acknowledged prognostic value of FDG PET imaging. By contrast, the prognostic value of PSMA PET imaging is independent of the expression of its encoding gene FOLH1. Instead, it is influenced by the protein docking to the cell membrane, regulating its accessibility to tracer binding.


Subject(s)
Fluorodeoxyglucose F18 , Positron-Emission Tomography , Prostatic Neoplasms , Humans , Male , Glucose/metabolism , Positron-Emission Tomography/methods , Prostate/diagnostic imaging , Prostate/metabolism , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Machine Learning
8.
Cortex ; 147: 72-82, 2022 02.
Article in English | MEDLINE | ID: mdl-35026556

ABSTRACT

Negation applied to action contexts reduces the activation of the motor system. According to the Reusing Inhibition for Negation (RIN) hypothesis, such "disembodiment" effect occurs because understanding negations engages the reuse of inhibitory control mechanisms. Here, we investigated whether the right inferior frontal gyrus (rIFG) - a key area of the inhibitory control system - contributes to primary motor cortex (M1) processing of negated action-sentences. Using a perturb-and-measure paradigm, we applied off-line low-frequency repetitive TMS (rTMS) over the rIFG, before performing a reading task involving action and attentional sentences presented in both affirmative or negative form. During the reading task, motor excitability was assessed by recording motor-evoked potentials (MEPs) induced by single-pulse TMS (spTMS) over the left M1, at two loci in the sentence: the verb or the object. Results show that after sham stimulation (baseline), motor excitability measured on the verb, was reduced for negative, compared to affirmative action sentences. Crucially, neuromodulation of rIFG suppressed this inhibitory effect of negation, since motor excitability was equaled for negative and affirmative action sentences. As expected, no effect of negation was observed for attentional sentences or when the pulse was delivered over the object. Our study confirms that understanding negative action sentences inhibits M1. This effect took place at an early stage of semantic processing (i.e., while processing the verb in our task), and faded at a later time-point. Critically, by highlighting a causal role of rIFG in this motor inhibition, we provide direct neurophysiological support to the RIN hypothesis.


Subject(s)
Evoked Potentials, Motor , Inhibition, Psychological , Evoked Potentials, Motor/physiology , Humans , Language , Neural Inhibition , Semantics , Transcranial Magnetic Stimulation
9.
J Anesth Analg Crit Care ; 2(1): 9, 2022 Feb 12.
Article in English | MEDLINE | ID: mdl-37386540

ABSTRACT

We aim to develop evidence-based recommendations for intensivists caring for children admitted to intensive care units and requiring analgesia and sedation. A panel of national paediatric intensivists expert in the field of analgesia and sedation and other specialists (a paediatrician, a neuropsychiatrist, a psychologist, a neurologist, a pharmacologist, an anaesthesiologist, two critical care nurses, a methodologist) started in 2018, a 2-year process. Three meetings and one electronic-based discussion were dedicated to the development of the recommendations (presentation of the project, selection of research questions, overview of text related to the research questions, discussion of recommendations). A telematic anonymous consultation was adopted to reach the final agreement on recommendations. A formal conflict-of-interest declaration was obtained from all the authors. Eight areas of direct interest and one additional topic were considered to identify the best available evidence and to develop the recommendations using the Evidence-to-Decision framework according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. For each recommendation, the level of evidence, the strength of the recommendation, the benefits, the harms and the risks, the benefit/harm balance, the intentional vagueness, the values judgement, the exclusions, the difference of the opinions, the knowledge gaps, and the research opportunities were reported. The panel produced 17 recommendations. Nine were evaluated as strong, 3 as moderate, and 5 as weak. Conclusion: a panel of national experts achieved consensus regarding recommendations for the best care in terms of analgesia and sedation in critically ill children.

10.
Antioxidants (Basel) ; 12(1)2022 Dec 26.
Article in English | MEDLINE | ID: mdl-36670904

ABSTRACT

Cancer utilization of large glutamine equivalents contributes to diverging glucose-6-P flux toward the pentose phosphate shunt (PPP) to feed the building blocks and the antioxidant responses of rapidly proliferating cells. In addition to the well-acknowledged cytosolic pathway, cancer cells also run a largely independent PPP, triggered by hexose-6P-dehydrogenase within the endoplasmic reticulum (ER), whose activity is mandatory for the integrity of ER-mitochondria networking. To verify whether this reticular metabolism is dependent on glutamine levels, we complemented the metabolomic characterization of intermediates of the glucose metabolism and tricarboxylic acid cycle with the estimation of proliferating activity, energy metabolism, redox damage, and mitochondrial function in two breast cancer cell lines. ER-PPP activity and its determinants were estimated by the ER accumulation of glucose analogs. Glutamine shortage decreased the proliferation rate despite increased ATP and NADH levels. It depleted NADPH reductive power and increased malondialdehyde content despite a marked increase in glucose-6P-dehydrogenase. This paradox was explained by the deceleration of ER-PPP favored by the decrease in hexose-6P-dehydrogenase expression coupled with the opposite response of its competitor enzyme glucose-6P-phosphatase. The decreased ER-PPP activity eventually hampered mitochondrial function and calcium exchanges. These data configure the ER-PPP as a powerful, unrecognized regulator of cancer cell metabolism and proliferation.

11.
Brain Sci ; 11(9)2021 Sep 13.
Article in English | MEDLINE | ID: mdl-34573224

ABSTRACT

The ability to rapidly process others' emotional signals is crucial for adaptive social interactions. However, to date it is still unclear how observing emotional facial expressions affects the reactivity of the human motor cortex. To provide insights on this issue, we employed single-pulse transcranial magnetic stimulation (TMS) to investigate corticospinal motor excitability. Healthy participants observed happy, fearful and neutral pictures of facial expressions while receiving TMS over the left or right motor cortex at 150 and 300 ms after picture onset. In the early phase (150 ms), we observed an enhancement of corticospinal excitability for the observation of happy and fearful emotional faces compared to neutral expressions specifically in the right hemisphere. Interindividual differences in the disposition to experience aversive feelings (personal distress) in interpersonal emotional contexts predicted the early increase in corticospinal excitability for emotional faces. No differences in corticospinal excitability were observed at the later time (300 ms) or in the left M1. These findings support the notion that emotion perception primes the body for action and highlights the role of the right hemisphere in implementing a rapid and transient facilitatory response to emotional arousing stimuli, such as emotional facial expressions.

12.
Cereb Cortex ; 31(3): 1569-1581, 2021 02 05.
Article in English | MEDLINE | ID: mdl-33136142

ABSTRACT

The embodied cognition approach to linguistic meaning posits that action language understanding is grounded in sensory-motor systems. However, evidence that the human motor cortex is necessary for action language memory is meager. To address this issue, in two groups of healthy individuals, we perturbed the left primary motor cortex (M1) by means of either anodal or cathodal transcranial direct current stimulation (tDCS), before participants had to memorize lists of manual action and attentional sentences. In each group, participants received sham and active tDCS in two separate sessions. Following anodal tDCS (a-tDCS), participants improved the recall of action sentences compared with sham tDCS. No similar effects were detected following cathodal tDCS (c-tDCS). Both a-tDCS and c-tDCS induced variable changes in motor excitability, as measured by motor-evoked potentials induced by transcranial magnetic stimulation. Remarkably, across groups, action-specific memory improvements were positively predicted by changes in motor excitability. We provide evidence that excitatory modulation of the motor cortex selectively improves performance in a task requiring comprehension and memory of action sentences. These findings indicate that M1 is necessary for accurate processing of linguistic meanings and thus provide causal evidence that high-order cognitive functions are grounded in the human motor system.


Subject(s)
Comprehension/physiology , Evoked Potentials, Motor/physiology , Memory/physiology , Motor Cortex/physiology , Transcranial Direct Current Stimulation , Adult , Female , Humans , Language , Male
13.
Cortex ; 132: 460-472, 2020 11.
Article in English | MEDLINE | ID: mdl-32950239

ABSTRACT

Non-invasive stimulation of the primary motor cortex (M1) modulates processing of decontextualized action words and sentences (i.e., verbal units denoting bodily motion). This suggests that language comprehension hinges on brain circuits mediating the bodily experiences evoked by verbal material. Yet, despite its relevance to constrain mechanistic language models, such a finding fails to reveal whether and how relevant circuits operate in the face of full-blown, everyday texts. Using a novel naturalistic discourse paradigm, we examined whether direct modulation of M1 excitability influences the grasping of narrated actions. Following random group assignment, participants received anodal transcranial direct current stimulation over the left M1, or sham stimulation of the same area, or anodal stimulation of the left ventrolateral prefrontal cortex. Immediately afterwards, they listened to action-laden and neutral stories and answered questions on information realized by verbs (denoting action and non-action processes) and circumstances (conveying locative or temporal details). Anodal stimulation of the left M1 selectively decreased outcomes on action-relative to non-action information -a pattern that discriminated between stimulated and sham participants with 74% accuracy. This result was particular to M1 and held irrespective of the subjects' working memory and vocabulary skills, further attesting to its specificity. Our findings suggest that offline modulation of motor-network excitability might lead to transient unavailability of putative resources needed to evoke actions in naturalistic texts, opening promising avenues for the language embodiment framework.


Subject(s)
Motor Cortex , Transcranial Direct Current Stimulation , Electrodes , Hand Strength , Humans , Memory, Short-Term
14.
Acta Neuropathol Commun ; 8(1): 126, 2020 08 06.
Article in English | MEDLINE | ID: mdl-32762731

ABSTRACT

With evidence supporting the prion-like spreading of extracellular tau as a mechanism for the initiation and progression of Alzheimer's disease (AD), immunotherapy has emerged as a potential disease-modifying strategy to target tau. Many studies have proven effective to clear pathological tau species in animal models of AD, and several clinical trials using conventional immunotherapy with anti-tau native antibodies are currently active. We have previously generated a vectorized scFv derived from the conformation-dependent anti-tau antibody MC1, scFvMC1, and demonstrated that its intracranial injection was able to prevent tau pathology in adult tau mice. Here, we show that, in a prevention paradigm and in two different tau transgenic models (JNPL3 and P301S), a one-time intramuscular injection of AAV1-scFvMC1 generated a long-lasting peripheral source of anti-tau scFvMC1 and significantly reduced insoluble and soluble tau species in the brain. Moreover, our data showed that scFvMC1 was internalized by the microglia, in the absence of overt inflammation. This study demonstrates the efficacy of intramuscular delivery of vectorized scFv to target tau, and suggests a new potential application to treat AD and the other tauopathies.


Subject(s)
Alzheimer Disease/pathology , Immunotherapy/methods , Single-Chain Antibodies/administration & dosage , tau Proteins/antagonists & inhibitors , Adenoviridae , Animals , Disease Models, Animal , Genetic Vectors , Humans , Injections, Intramuscular , Mice , Mice, Transgenic
15.
Neuropsychologia ; 146: 107541, 2020 09.
Article in English | MEDLINE | ID: mdl-32593723

ABSTRACT

The early response to emotional stimuli involves a transient suppression of motor reactivity to favor monitoring of emotionally relevant information. Using transcranial magnetic stimulation (TMS), we have previously shown that viewing emotional body postures induces an early and transient reduction in motor excitability. Yet, it remains unclear whether early motor responses to emotional bodies are automatic or influenced by top-down factors such as task- or gender-related effects. To address these issue, we administered TMS over the right motor cortex (M1) during observation of still pictures of fearful expressions, happy expressions, neutral movements and neutral static body postures, and recorded motor-evoked potentials (MEPs) at an early phase of processing (i.e., at 100-125 ms from stimulus onset). To test gender-related effects, we presented male and female models to male and female participants. To test task-related effects, we asked participants to categorize the different body postures into either four (4AFC: fearful, happy, neutral movements, or static postures) or two distinct categories (2AFC: emotional or neutral postures). Results showed a reduction of MEPs for fearful and happy body postures relative to neutral movements and static postures. This motor suppression was not influenced by the gender of the actor, the gender of the observer, or the task performed. These findings indicate that early motor responses to observed human body postures are affected by the type of expression displayed by the observed model more than by task- or gender-related effects, suggesting these responses may be relatively automatic.


Subject(s)
Emotions , Evoked Potentials, Motor , Motor Cortex/physiology , Posture , Sex Characteristics , Female , Humans , Male , Movement , Transcranial Magnetic Stimulation , Young Adult
16.
Pediatr Crit Care Med ; 21(7): 625-636, 2020 07.
Article in English | MEDLINE | ID: mdl-32224830

ABSTRACT

OBJECTIVES: We sought to evaluate dexmedetomidine efficacy in assuring comfort and sparing conventional drugs when used for prolonged sedation (≥24 hr) in critically ill patients, by using validated clinical scores while systematically collecting drug dosages. We also evaluated the safety profile of dexmedetomidine and the risk factors associated with adverse events. DESIGN: Observational prospective study. SETTING: Nine tertiary-care PICUs. PATIENTS: Patients less than 18 years who received dexmedetomidine for greater than or equal to 24 hours between January 2016 and December 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-hundred sixty-three patients (median age, 13 mo; interquartile range, 4-71 mo) were enrolled. The main indication for dexmedetomidine use was as an adjuvant for drug-sparing (42%). Twenty-three patients (14%) received dexmedetomidine as monotherapy. Seven percent of patients received a loading dose. The median infusion duration was 108 hours (interquartile range, 60-168 hr), with dosages between 0.4 (interquartile range, 0.3-0.5) and 0.8 µg/kg/hr (interquartile range, 0.6-1.2 µg/kg/hr). At 24 hours of dexmedetomidine infusion, values of COMFORT-B Scale (n = 114), Withdrawal Assessment Tool-1 (n = 43) and Cornell Assessment of Pediatric Delirum (n = 6) were significantly decreased compared with values registered immediately pre dexmedetomidine (p < 0.001, p < 0.001, p = 0.027). Dosages/kg/hr of benzodiazepines, opioids, propofol, and ketamine were also significantly decreased (p < 0.001, p < 0.001, p = 0.001, p = 0.027). The infusion was weaned off in 85% of patients, over a median time of 36 hours (interquartile range, 12-48 hr), and abruptly discontinued in 15% of them. Thirty-seven percent of patients showed hemodynamic changes, and 9% displayed hemodynamic adverse events that required intervention (dose reduction in 79% of cases). A multivariate logistic regression model showed that a loading dose (odds ratio, 4.8; CI, 1.2-18.7) and dosages greater than 1.2 µg/kg/hr (odds ratio, 5.4; CI, 1.9-15.2) increased the odds of hemodynamic changes. CONCLUSIONS: Dexmedetomidine used for prolonged sedation assures comfort, spares use of other sedation drugs, and helps to attenuate withdrawal syndrome and delirium symptoms. Adverse events are mainly hemodynamic and are reversible following dose reduction. A loading dose and higher infusion dosages are independent risk factors for hemodynamic adverse events.


Subject(s)
Dexmedetomidine , Adolescent , Child , Dexmedetomidine/adverse effects , Humans , Hypnotics and Sedatives/adverse effects , Intensive Care Units, Pediatric , Prospective Studies , Retrospective Studies
17.
Trials ; 20(1): 710, 2019 Dec 11.
Article in English | MEDLINE | ID: mdl-31829274

ABSTRACT

BACKGROUND: Prolonged treatment with analgesic and sedative drugs in the pediatric intensive care unit (PICU) may lead to undesirable effects such as dependence and tolerance. Moreover, during analgosedation weaning, patients may develop clinical signs of withdrawal, known as withdrawal syndrome (WS). Some studies indicate that dexmedetomidine, a selective α2-adrenoceptor agonist, may be useful to prevent WS, but no clear evidence supports these data. The aims of the present study are to evaluate the efficacy of dexmedetomidine in reducing the occurrence of WS during analgosedation weaning, and to clearly assess its safety. METHODS: We will perform an adaptive, multicenter, randomized, double-blind, placebo-controlled trial. Patients aged < 18 years receiving continuous intravenous analgosedation treatment for at least 5 days and presenting with clinical conditions that allow analgosedation weaning will be randomly assigned to treatment A (dexmedetomidine) or treatment B (placebo). The treatment will be started 24 h before the analgosedation weaning at 0.4 µg/kg/h, increased by 0.2 µg/kg/h per hour up to 0.8 µg/kg/h (neonate: 0.2 µg/kg/h, increased by 0.1 µg/kg/h per hour up to 0.4 µg/kg/h) and continued throughout the whole weaning time. The primary endpoint is the efficacy of the treatment, defined by the reduction in the WS rate among patients treated with dexmedetomidine compared with patients treated with placebo. Safety will be assessed by collecting any potentially related adverse event. The sample size assuring a power of 90% is 77 patients for each group (total N = 154 patients). The study was approved by the Ethics Committee of the University-Hospital S.Orsola-Malpighi of Bologna on 22 March 2017. DISCUSSION: The present trial will allow us to clearly assess the efficacy of dexmedetomidine in reducing the occurrence of WS during weaning from analgosedation drugs. In addition, the study will provide a unique insight into the safety profile of dexmedetomidine. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03645603. Registered on 24 August 2018. EudraCT, 2015-002114-80. Retrospectively registered on 2 January 2019.


Subject(s)
Adrenergic alpha-2 Receptor Agonists/administration & dosage , Analgesics, Opioid/adverse effects , Benzodiazepines/adverse effects , Dexmedetomidine/administration & dosage , Hypnotics and Sedatives/adverse effects , Intensive Care Units, Pediatric , Opioid-Related Disorders/prevention & control , Substance Withdrawal Syndrome/prevention & control , Adaptive Clinical Trials as Topic , Adolescent , Adrenergic alpha-2 Receptor Agonists/adverse effects , Age Factors , Analgesics, Opioid/administration & dosage , Benzodiazepines/administration & dosage , Child , Child, Preschool , Dexmedetomidine/adverse effects , Double-Blind Method , Drug Administration Schedule , Drug Tolerance , Female , Humans , Hypnotics and Sedatives/administration & dosage , Infant , Infant, Newborn , Infusions, Intravenous , Italy , Male , Multicenter Studies as Topic , Opioid-Related Disorders/diagnosis , Opioid-Related Disorders/etiology , Randomized Controlled Trials as Topic , Substance Withdrawal Syndrome/diagnosis , Substance Withdrawal Syndrome/etiology , Time Factors , Treatment Outcome
18.
Animals (Basel) ; 9(11)2019 Nov 01.
Article in English | MEDLINE | ID: mdl-31683800

ABSTRACT

This experiment aimed to investigate the possibility to increase the carcass weight of dairy breed lambs and produce moderate-fat meat by applying inexpensive feeding strategies based on restriction and through the use of a fibrous byproduct such as the durum wheat bran (DWB). Sixty-five 45-day-old lambs of the Valle del Belice breed, divided into 6 groups, were fed alfalfa hay supplemented with concentrate feeds including DWB at 0% or 20% (DWB0, DWB20), supplied ad libitum (L) or restricted at 75% (R), and slaughtered at 90 or 120 days of age. The groups were as follows: DWB0-90L (n = 14), DWB20-90L (n = 14), DWB0-120R (n = 10), DWB20-120R (n = 9), DWB0-120L (n = 9), DWB20-120L (n = 9). The diet did not affect feed intake, growth or carcass weight of lambs fed ad libitum, whereas 120-day-old lambs fed DWB associated to restriction showed the lowest weight gain (105 vs. 170, 185 and 190 g/day in DWD20-120R, DWB0-120R, DWB0-120L and DWB20-120L; p = 0.04). The incidence of fat tissue in the hind leg increased (p < 0.0001) from 90L (5.82 and 5.45% with DWB0 and DWB20) to 120R (8.80 and 8.43% with DWB0 and DWB20) and 120L lambs (10.7 and 11.8% with DWB0 and DWB20). Older lambs' meat, compared to that of 90L lambs, showed analogous levels of intramuscular fat, higher water retention, tenderness and lightness, and a more intense red colour. In meat from 120-day-old lambs, DWB intake tended to reduce the fat level (p = 0.009) and increased polyphenol content (1.10 vs. 1.62, and 1.02 vs. 1.65 g GAE/kg dry matter (DM) in 120R and 120L lambs; p = 0.02), antioxidant capacity (12.8 vs. 14.9, and 12.8 vs. 15.7 mmol trolox eq/kg DM in 120R and 120L lambs; p = 0.02), and the presence of n-3 polyunsaturated fatty acids (FA) (1.61 vs. 2.81, and 1.43 vs. 2.61 g/100 g FA in 120R and 120L lambs; p = 0.007), thereby improving the meat's health properties. The panelists perceived the effects of DWB inclusion as well as the feeding level with triangle tests.

19.
Minerva Anestesiol ; 85(12): 1334-1345, 2019 12.
Article in English | MEDLINE | ID: mdl-31630510

ABSTRACT

Intranasal dexmedetomidine, although still off-label, recently boasted an increasing consensus for different uses, namely, in diagnostic non-painful procedures, in painful procedures and in surgical premedication. However, at present, there is no consensus regarding indications, dosage and timing for administration. This article aims to provide a comprehensive literature analysis and summarize the more recent evidence of research on pediatric intranasal dexmedetomidine, in the effort to better delineate usefulness and limits for each specific indication. In summary, available pediatric evidence confirms efficacy and safety of dexmedetomidine for intranasal administration. Pharmacological profile for the various pediatric ages and procedures still needs quality studies and pharmacokinetic in-depth analysis.


Subject(s)
Analgesics, Non-Narcotic/administration & dosage , Dexmedetomidine/administration & dosage , Administration, Intranasal , Analgesics, Non-Narcotic/adverse effects , Analgesics, Non-Narcotic/pharmacology , Child , Dexmedetomidine/adverse effects , Dexmedetomidine/pharmacology , Humans , Treatment Outcome
20.
Animals (Basel) ; 9(9)2019 Sep 18.
Article in English | MEDLINE | ID: mdl-31540437

ABSTRACT

Durum wheat bran (DWB) is a by-product mostly used in feeding ruminants, contributing to decrease in the utilization of feeds suitable as foods for human consumption, thus improving the sustainability of livestock production. However, the potential benefits of DWB, due to its content in phenolic acids, mainly consisting of ferulic acid with antioxidant properties, have not been well clarified yet. Accordingly, in this experiment, 36 lactating cows divided into three groups received, over a period of 100 days, one of three concentrates including DWB at 0% (DWB0), 10% (DWB10), or 20% (DWB20). The concentrates were formulated to be isoproteic and isoenergetic and, to balance the higher fiber content of the concentrates with DWB, the hay in the diets was slightly reduced. During the trial, the group feed intake and the individual milk production were monitored, and cheese was made with bulk milk from each group. Milk yield and microbiological characteristics of milk and cheese were similar among groups, indicating no DWB effect on cows performance and fermentation process. Milk from DWB20 group resulted slightly higher in casein and curd firmness (a2r). In cows fed DWB, the higher polyphenol intake was responsible for higher blood contents of these bioactive compounds, that seemed to have contributed in reducing the level of reactive oxygen metabolites (ROMs), which were higher in DWB0 cows. DWB20 cheeses showed a higher polyphenol content, lower number of peroxides, and higher antioxidant capacity than DWB0 cheeses. DWB20 and DWB10 diets resulted less expensive. In addition, the DWB20 group showed the best indexes heFCE (human edible feed conversion efficiency = milk/human edible feed) and NFP (net food production = milk - human edible food), expressed as crude protein or gross energy. In conclusion, the DWB fed to dairy cows at 12% of diet dry matter (DM) can lead to benefits, such as the improvement of oxidative status of cows, milk quality, shelf-life, and functional properties of cheese, and might contribute to reduce the feeding cost and limit the human-animal competition for feeding sources.

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