Sex-specific interactions between stress axis and redox balance are associated with internalizing symptoms and brain white matter microstructure in adolescents.

Adolescence is marked by the maturation of systems involved in emotional regulation and by an increased risk for internalizing disorders (anxiety/depression), especially in females. Hypothalamic-pituitary-adrenal (HPA)-axis function and redox homeostasis (balance between reactive oxygen species and antioxidants) have both been associated with internalizing disorders and may represent critical factors for the development of brain networks of emotional regulation. However, sex-specific interactions between these factors and internalizing symptoms and their link with brain maturation remain unexplored. We investigated in a cohort of adolescents aged 13-15 from the general population (n = 69) whether sex-differences in internalizing symptoms were associated with the glutathione (GSH)-redox cycle homeostasis and HPA-axis function and if these parameters were associated with brain white matter microstructure development. Female adolescents displayed higher levels of internalizing symptoms, GSH-peroxidase (GPx) activity and cortisol/11-deoxycortisol ratio than males. There was a strong correlation between GPx and GSH-reductase (Gred) activities in females only. The cortisol/11-deoxycortisol ratio, related to the HPA-axis activity, was associated with internalizing symptoms in both sexes, whereas GPx activity was associated with internalizing symptoms in females specifically. The cortisol/11-deoxycortisol ratio mediated sex-differences in internalizing symptoms and the association between anxiety and GPx activity in females specifically. In females, GPx activity was positively associated with generalized fractional anisotropy in widespread white matter brain regions. We found that higher levels of internalizing symptoms in female adolescents than in males relate to sex-differences in HPA-axis function. In females, our results suggest an important interplay between HPA-axis function and GSH-homeostasis, a parameter strongly associated with brain white matter microstructure.

Toward Continuum Robot Tentacles for Lung Interventions: Exploring Folding Support Disks.

Toward the future goal of creating a lung surgery system featuring multiple tentacle-like robots, we present a new folding concept for continuum robots that enables them to squeeze through openings smaller than the robot's nominal diameter (e.g., the narrow space between adjacent ribs). This is facilitated by making the disks along the robot's backbone foldable. We also demonstrate that such a robot can feature not only straight, but also curved tendon routing paths, thereby achieving a diverse family of conformations. We find that the foldable robot performs comparably, from a kinematic perspective, to an identical non-folding continuum robot at varying deployment lengths. This work paves the way for future applications with a continuum robot that can fold and fit through smaller openings, with the potential to reduce invasiveness during surgical tasks.

Design and Integration of a Texting Tool to Keep Patients' Family Members Updated During Hospitalization: Family Members' Perspectives.

While there is an evolving literature on the benefits of texting and patient-centered technologies, texting initiatives have not focused on family members. We sought to identify patients' family members' perspectives on facilitators and barriers to using 1 digital texting innovation to promote family-centered care during patients' hospitalizations. This qualitative study was conducted at a tertiary care center in Houston, consisting of 7 hospitals (1 academic hospital and 6 community hospitals), involving analyzation of 3137 comments from family members who used the digital texting technology. Thematic analysis methods were used. The data analysis for loved ones' feedback resulted in 4 themes as facilitators: (1) inpatient text messaging keeps loved ones updated and connected (n = 611); (2) inpatient text messaging allows for stronger continuity of communication (n = 69); (3) messaging promotes a sense of staff compassion and service (n = 245); and (4) messaging reduces phone calls (n = 65). The data analysis resulted in 4 themes as barriers to text messaging helpfulness: (1) messages could feel generic (n = 31); (2) inpatient texting was not needed if all loved ones were regularly at bedside (n = 6); (3) messages could have a perceived delay (n = 37); and (4) security features could impact convenience (n = 29). Our findings indicate that family members and loved ones value inpatient text messages, not only for the information the messages provide, but also because the act of writing text messages and preparing loved ones shows inclusiveness, compassion, and family-centered care.

Design and Integration of a Texting Tool to Keep Patients' Family Members Updated During Hospitalization: Clinicians' Perspectives.

An important gap in the literature is how clinicians feel about patient-centered technologies and how clinicians experience patient-centered technologies in their workflows. Our goal was to identify clinician users' perspectives on facilitators (pros) and barriers (cons) to using 1 digital texting innovation to promote family centered care during patients' hospitalizations. This qualitative study was conducted at a tertiary care center in Houston, consisting of 7 hospitals (1 academic hospital and 6 community hospitals), involving analyzation of 3 focus groups of 18 physicians, 5 advanced practice providers, and 10 nurse directors and managers, as well as a content analysis of 156 real-time alerts signaling family dissatisfaction on the nursing unit/floor. Thematic analysis methods were used. We selected these participants by attending their regularly scheduled service-line meetings. Clinician feedback from focus groups resulted in 3 themes as facilitators: (a) texting platforms must be integrated within the electronic medical record; (b) texting reduces outgoing phone calls; (c) texting reduces incoming family phone calls. Clinician feedback resulted in 3 themes as barriers: (a) best practice alerts can be disruptive; (b) real-time alerts can create hopelessness; and (c) scale-up is challenging. The analyzation of facilitators (pros) and barriers (cons) pertains only to the clinician's feedback. We also analyzed real-time alerts signaling family dissatisfaction (defined as "service recovery escalation" throughout this manuscript). The most common selection for the source of family dissatisfaction, as reflected through the real-time alerts was, "I haven't heard from physicians enough," appearing in 52 out of 156 alerts (33%). The second most common selection for the source of dissatisfaction was "perceived inconsistent or incomplete information provided by team members," which was selected in 48 cases (31%). Our findings indicate that clinicians value inpatient texting, not only for its ability to quickly relay updates to multiple family members with 1 click, but also because, when used intentionally and meaningfully, texting decreases family phone calls.

Randomized controlled trial of a mindfulness-based intervention in adolescents from the general population: The Mindfulteen neuroimaging study protocol.

AIM: Adolescence is a period of vulnerability to stress. Increased anxiety during this period has been associated with the later development of mental disorders, hence the growing interest for interventions that could decrease stress reactivity and improve cognitive control in adolescents. Mindfulness-based interventions have demonstrated their efficacy on stress reactivity and anxiety in adults, but evidence is lacking in youth. METHODS: The Mindfulteen Study is a 3-year longitudinal cohort with a nested randomized controlled trial examining the effectiveness of mindfulness-based interventions for adolescents. Young adolescents from the general population, aged between 13 and 15 years old, with no history of current mental health disorder (apart from past mood disorders or current anxiety disorders) are included and stratified into low or high anxiety based on trait anxiety scores before being randomized to early or late 8-week intervention groups. Primary outcomes are based on neuroimaging data (i.e., structural and functional measures in the cortico-limbic network) while secondary outcomes are psychological (i.e., anxiety and stress-associated dimensions) and biological (i.e., cortisol, inflammatory and redox markers). Assessments are performed at baseline, immediately after intervention or waiting time and after 18 months of intervention. CONCLUSION: To the best of our knowledge, this is the first randomized controlled trail examining the effect of a mindfulness-based intervention in young adolescents from the general population based on the measurement and analyses of psychological, neuroimaging and biological data.

Otolaryngology Manifestations of Primary Ciliary Dyskinesia: A Multicenter Study.

OBJECTIVE: This project aims to prospectively and objectively assess otolaryngological manifestations and quality of life of children with primary ciliary dyskinesia (PCD) and compare these findings with healthy pediatric controls. STUDY DESIGN: Cross-sectional. SETTING: Two high-volume pediatric PCD specialty centers. METHODS: Standardized clinical assessment; Sino-Nasal Outcome Test 22 (SNOT-22); Hearing Environment and Reflection Quality of Life (HEAR-QL); Reflux Symptom Index (RSI); standardized physical examination of the sinonasal, laryngeal, and otological systems; and investigations including pure-tone audiograms (PTAs) and sinonasal cultures were collected. RESULTS: Forty-seven children with PCD and 25 control participants were recruited. Children with PCD had more upper airway symptoms than healthy children. They had significantly higher scores in both SNOT-22 and RSI, indicating worse sinonasal and reflux symptoms, with worse quality of life on the HEAR-QL index compared to healthy children (P < .05). Fifty-two percent of children with PCD-related hearing loss were not aware of their hearing deficit that was present on audiological assessment, and only 23% of children who had ventilation tubes had chronic otorrhea, most of which was easily controlled with ototopic drops. Furthermore, although all children with PCD had chronic rhinosinusitis, only 36% of them were using topical nasal treatment. The most common bacteria cultured from the middle meatus were Staphylococcus aureus in 11 of 47 (23%), followed by Streptococcus pneumoniae in 10 of 47 (21%). CONCLUSION: This multisite cohort highlights the importance of otolaryngology involvement in the management of children with PCD. More rigorous otolaryngological management may lead to reductions in overall morbidity and improve quality of life for children with PCD.

Improving executive, behavioural and socio-emotional competences in very preterm young adolescents through a mindfulness-based intervention: Study protocol and feasibility.

BACKGROUND: Very preterm (VPT) children and adolescents show executive, behavioural and socio-emotional difficulties that persist into adulthood. Despite the promising role of mindfulness-based intervention (MBI) in improving theses competences in children and adolescents, the effectiveness of an MBI has not been assessed in a VPT population so far. AIMS: To describe the protocol and to evaluate the feasibility and acceptability of a clinical trial on an 8-week MBI program to enhance executive and socio-emotional competences in a cohort of VPT young adolescents. STUDY DESIGN: A randomised controlled trial (RCT) and a pre-post intervention designs. PARTICIPANTS: 164 VPT young adolescents from 10 to 14 years old, born before 32 gestational weeks, without major intellectual, sensory or physical impairments, and attending mainstream school, were invited to participate in an 8-week MBI program. OUTCOME MEASURES: Completion rate of the study was recorded. Acceptability, satisfaction and attendance measures of the MBI were collected using self-reported questionnaires and registration of attendance. RESULTS: Of the 63 participants who were enrolled in the study (38.2% of families invited to participate), 52 (82.5%) completed all assessments. Acceptability was high as shown by the high attendance rate in the sessions and the feedback evaluation questionnaire. CONCLUSIONS: Our findings suggest that an MBI is feasible to implement and show a high acceptability among participants. The use of an RCT design in our study constitutes the gold standard for testing the efficacy of such intervention in VPT young adolescents. If effective, the MBI program could potentially be a valuable tool for improving executive and socio-emotional competences in the vulnerable VPT population. TRIAL REGISTRATION: ClinicalTrials, NCT04638101. Registered 19 November 2020 - retrospectively registered, https://clinicaltrials.gov/show/NCT04638101.

[Mindfulness based interventions for children and adolescents]. / Interventions basées sur la pleine conscience pour les enfants et les adolescents.

Mindfulness based interventions (MBI) are widely available to adults. Programs are also offered to children and adolescents. Interventions in school and clinical settings are increasingly being published in scientific literature. In the school context, the effects are promising on psychological health, such as stress, anxiety, depression or externalized behaviours, and on executive functions, attention, and socio-emotional skills. In the clinical context, MBI has a particular effect on stress/anxiety and depression as well as on the key symptoms of Attention Deficit Hyperactivity Disorder. These results are very encouraging, but all meta-analyses and literature reviews nevertheless emphasize the need for studies with robust methodology before proposing MBI on a large scale for this population.

Les interventions basées sur la pleine conscience (MBI) sont de plus en plus proposées aux enfants et aux adolescents et font l'objet de nombreuses publications scientifiques. Dans le contexte scolaire, les effets sont prometteurs sur la santé psychologique, comme le stress, l'anxiété, la dépression ou les comportements externalisés et sur les fonctions exécutives, l'attention, et les compétences socioémotionnelles. Dans le contexte clinique, les MBI ont un effet en particulier sur le stress/l'anxiété et la dépression ainsi que sur les symptômes clés du trouble du déficit d'attention avec hyperactivité. Ces résultats sont très encourageants mais toutes les méta-analyses et les revues de la littérature soulignent néanmoins la nécessité de faire des études à la méthodologie robuste avant de proposer des MBI à large échelle.

Influence of metabolic syndrome on cerebral perfusion and cognition.

Vascular cognitive impairment (VCI) is associated with chronic cerebral hypoperfusion (CCH) and memory deficits, and often occurs concurrently with metabolic syndrome (MetS). Despite their common occurrence, it is unknown whether CCH and MetS act synergistically to exacerbate VCI-associated pathology. Here, using male Sprague-Dawley rats, we examined the effects of a clinically relevant model of adolescent-onset MetS and adult-onset CCH on neuro-vascular outcomes, combining a cafeteria diet with a 2-vessel occlusion (2VO) model. Using longitudinal imaging, histology, and behavioural assessments, we identified several features of MetS and CCH including reduced cerebral blood volume, white matter atrophy, alterations in hippocampal cell density, and memory impairment. Furthermore, we identified a number of significant associations, potentially predictive of MetS and pathophysiological outcomes. White matter volume was positively correlated to HDL cholesterol; hippocampal cell density was negatively correlated to fasted blood glucose; cerebral blood flow and volume was negatively predicted by the combination of 2VO surgery and increased fasted blood glucose. These results emphasize the importance of including comorbid conditions when modeling VCI, and they outline a highly translational preclinical model that could be used to investigate potential interventions to mitigate VCI-associated pathology and cognitive decline.

Does Stroke Rehabilitation Really Matter? Part B: An Algorithm for Prescribing an Effective Intensity of Rehabilitation.

BACKGROUND: The proportional recovery rule suggests that current rehabilitation practices may have limited ability to influence stroke recovery. However, the appropriate intensity of rehabilitation needed to achieve recovery remains unknown. Similarities between rodent and human recovery biomarkers may allow determination of rehabilitation thresholds necessary to activate endogenous biological recovery processes. OBJECTIVE: We determined the relative influence that clinically relevant biomarkers of stroke recovery exert on functional outcome. These biomarkers were then used to generate an algorithm that prescribes individualized intensities of rehabilitation necessary for recovery of function. METHODS: A retrospective cohort of 593 male Sprague-Dawley rats was used to identify biomarkers that best predicted poststroke change in pellet retrieval in the Montoya staircase-reaching task using multiple linear regression. Prospective manipulation of these factors using endothelin-1-induced stroke (n = 49) was used to validate the model. RESULTS: Rehabilitation was necessary to reliably predict recovery across the continuum of stroke severity. As infarct volume and initial impairment increased, more intensive rehabilitation was required to engage recovery. In this model, we prescribed the specific dose of daily rehabilitation required for rats to achieve significant motor recovery using the biomarkers of initial poststroke impairment and infarct volume. CONCLUSIONS: Our algorithm demonstrates an individualized approach to stroke rehabilitation, wherein imaging and functional performance measures can be used to develop an optimized rehabilitation paradigm for rats, particularly those with severe impairments. Exploring this approach in human patients could lead to an increase in the proportion of individuals experiencing recovery of lost motor function poststroke.

Reduced Cerebrovascular Reactivity and Increased Resting Cerebral Perfusion in Rats Exposed to a Cafeteria Diet.

To better understand the effects of a diet high in fat, sugar, and sodium on cerebrovascular function, Sprague Dawley rats were chronically exposed to a Cafeteria diet. Resting cerebral perfusion and cerebrovascular reactivity was quantified using continuous arterial spin labeling (CASL) magnetic resonance imaging (MRI). In addition, structural changes to the cerebrovasculature and susceptibility to ischemic lesion were examined. Compared to control animals fed standard chow (SD), Cafeteria diet (CAF) rats exhibited increased resting brain perfusion in the hippocampus and reduced cerebrovascular reactivity in response to 10% inspired CO2 challenges in both the hippocampus and the neocortex. CAF rats switched to chow for one month (SWT) exhibited improved resting perfusion in the hippocampus as well as improved cerebrovascular reactivity in the neocortex. However, the diet switch did not correct cerebrovascular reactivity in the hippocampus. These changes were not accompanied by alterations in the structural integrity of the cerebral microvasculature, examined using rat endothelial cell antigen-1 (RECA-1) and immunoglobulin G (IgG) immunostaining. Also, the extent of tissue damage induced by endothelin-1 injection into sensorimotor cortex was not affected by the Cafeteria diet. These results demonstrate that short-term consumption of an ultra-processed diet reduces cerebrovascular reactivity. This effect persists after dietary normalization despite recovery of peripheral symptomatology.

Clinical presentation and airway management of tracheal atresia: A systematic review.

OBJECTIVES: Tracheal atresia (TA) is a rare congenital condition that typically requires an unexpected and emergent resuscitation in the delivery room. The mortality rate associated is very high, with only a few long-term survival cases reported. We describe the findings of a systematic review on the clinical presentation and airway management of TA. METHODS: Using the keywords "tracheal atresia", "tracheal agenesis" and "tracheal hypoplasia" a search through Embase and Pubmed databases was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Articles published from 1950 to 2015 in English, French, Italian, Portuguese and Spanish were included. Exclusion criteria were cases of stillborn, and unclear diagnosis or outcome. RESULTS: 149 cases of TA were identified after reviewing 1125 initial references. There was a male preponderance (65%), and associated malformations were described in 94.2% of patients. Prenatal ultrasound was abnormal in 56.3% of cases, with polyhydramnios being the most common finding. The most frequent type of TA was Faro Type C. 94 (41.3%) patients did not survive beyond the first 24 h of life. Only 13 (8.4%) patients survived more than three months of life, after undergoing a variety of surgical approaches. CONCLUSION: This review, which to our knowledge is the largest one to date, confirms that TA is a rare malformation, occurs more frequently in males, and has a very high mortality rate. Depending on the presence and type of concomitant malformation, as well of the length of the remaining trachea, different surgical management options are described.

A physiological characterization of the Cafeteria diet model of metabolic syndrome in the rat.

Many promising findings from pre-clinical research have failed to translate to the clinic due to their inability to incorporate human disease co-morbidity. A variety of rodent diets and feeding durations are currently used in models of human metabolic syndrome, obesity and diabetes. One model, the Cafeteria (CAF) diet, makes use of grocery store-purchased food items that more closely approximate the human ultra-processed diet than commercial high-fat or high-sugar rodent diets. The present study describes the development of metabolic syndrome in rats fed a CAF diet as well as the recovery of metabolic syndrome following a healthy "lifestyle" change. In addition, we explored the effects of CAF diet on spatial learning and memory and on neuroinflammation. Three-week old male Sprague-Dawley rats were fed a CAF diet for three months that consisted of 16 highly palatable human food items along with standard chow and a 12% sucrose solution to mimic soda consumption. Thereafter, a sub-group of CAF diet rats was switched to a chow diet (SWT) for one month. Both CAF and SWT groups were compared to control rats maintained on a standard chow diet (SD). Prior to the diet switch, CAF and SWT animals developed features akin to metabolic syndrome. Both groups of rats displayed significant abdominal obesity with increased visceral adiposity, hyperinsulinemia, glucose intolerance and dyslipidemia with elevated serum triglyceride levels and reduced HDL cholesterol. Switching to a chow diet for one month completely reversed these features in SWT animals. Although acquisition of the Barnes maze was not affected by the CAF diet, these animals exhibited greater hippocampal neuroinflammation compared to both SD and SWT rats as assessed by Iba1 staining. These results demonstrate that the CAF diet is very effective in creating metabolic syndrome with hippocampal inflammation in rats over a relatively short time span. This model may be of great heuristic importance in determining potential reversibility of metabolic and cerebrovascular pathologies across the lifespan and as a co-morbid factor in other disease models such as stroke.

Tracheoesophageal fistula: open versus endoscopic repair.

PURPOSE OF REVIEW: The management of primary or recurrent tracheoesophageal fistula (TEF) remains an important challenge for airway surgeons. RECENT FINDINGS: The accuracy of prenatal detection can be significantly improved in specialized centers. Routine preoperative and postoperative airway endoscopy is recommended to detect a proximal fistula and evaluate vocal cord motility. Minimally invasive thoracoscopic approaches have equal success and improved cosmesis and visualization as compared with thoracostomy. Novel open approaches for complex TEF include a transcervical, transtracheal approach, and slide tracheoplasty.Endoscopic closure of TEF carries less morbidity. Options include de-epithelialization of the tract, interposed material, and combinations. The mean operative time is 30 min; however multiple treatments are required (average 2.1). Use of continuous positive airway pressure in the immediate postoperative period was not associated with increased leak or recurrence. Children post-TEF repair continue to have frequent gastrointestinal and respiratory symptoms. SUMMARY: Prenatal diagnosis is beneficial both for prenatal counseling and for planning care. The ideal endoscopic approach is undecided but remains an interesting alternative to open surgery provided failures are anticipated and prompt repeated treatments initiated to preclude ongoing respiratory complications. Transtracheal approaches and slide tracheoplasty are well tolerated and effective in complex/recurrent cases. Long-term follow-up of patients with TEF is important.

Enriched rehabilitation promotes motor recovery in rats exposed to neonatal hypoxia-ischemia.

Despite continuous improvement in neonatology there is no clinically effective treatment for perinatal hypoxia ischemia (HI). Therefore, development of a new therapeutic intervention to minimize the resulting neurological consequences is urgently needed. The immature brain is highly responsive to environmental stimuli, such as environmental enrichment but a more effective paradigm is enriched rehabilitation (ER), which combines environmental enrichment with daily reach training. Another neurorestorative strategy to promote tissue repair and functional recovery is cyclosporine A (CsA). However, potential benefits of CsA after neonatal HI have yet to be investigated. The aim of this study was to investigate the effects of a combinational therapy of CsA and ER in attempts to promote cognitive and motor recovery in a rat model of perinatal hypoxic-ischemic injury. Seven-day old rats were submitted to the HI procedure and divided into 4 groups: CsA+Rehabilitation; CsA+NoRehabilitation; Vehicle+Rehabilitation; Vehicle+NoRehabilitation. Behavioural parameters were evaluated pre (experiment 1) and post 4 weeks of combinational therapy (experiment 2). Results of experiment 1 demonstrated reduced open field activity of HI animals and increased foot faults relative to shams in the ladder rung walking test. In experiment 2, we showed that ER facilitated acquisition of a staircase skilled-reaching task, increased number of zone crosses in open-field exploration and enhanced coordinated limb use during locomotion on the ladder rung task. There were no evident deficits in novel object recognition testing. Delayed administration of CsA, had no effect on functional recovery after neonatal HI. There was a significant reduction of cortical and hemispherical volume and hippocampal area, ipsilateral to arterial occlusion in HI animals; combinational therapy had no effect on these morphological measurements. In conclusion, the present study demonstrated that ER, but not CsA was the main contributor to enhanced recovery of motor ability after neonatal HI.

Lost in translation: rethinking approaches to stroke recovery.

Stroke is the second leading cause of death and the preeminent cause of neurological disability. Attempts to limit brain injury after ischemic stroke with clot-dissolving drugs have met with great success but their use remains limited due to a narrow therapeutic time window and concern over serious side effects. Unfortunately, the neuroprotective strategy failed in clinical trials. A more promising approach is to promote recovery of function in people affected by stroke. Following stroke, there is a heightened critical period of plasticity that appears to be receptive to exogenous interventions (e.g., delivery of growth factors) designed to enhance neuroplasticity processes important for recovery. An emerging concept is that combinational therapies appear much more effective than single interventions in improving stroke recovery. One of the most promising interventions, with clinical feasibility, is enriched rehabilitation, a combination of environmental enrichment and task-specific therapy.

Comparative study between fast and slow induction of propofol given by target-controlled infusion: expected propofol concentration at the effect site. Randomized controlled trial / Estudo comparativo entre indução rápida e lenta de propofol em infusão alvo-controlada: concentração de propofol prevista no local de ação. Ensaio clínico aleatório / Estudio comparativo entre inducción rápida y lenta de propofol en infusión objetivo-controlada: concentración de propofol prevista en la región de acción. Ensayo clínico aleatorizado

BACKGROUND AND OBJECTIVE: Studies have shown that the rate of propofol infusion may influence the predicted propofol concentration at the effect site (Es). The aim of this study was to evaluate the Es predicted by the Marsh pharmacokinetic model (ke0 0.26 min-1) in loss of consciousness during fast or slow induction. METHOD: The study included 28 patients randomly divided into two equal groups. In slow induction group (S), target-controlled infusion (TCI) of propofol with plasma, Marsh pharmacokinetic model (ke0 0.26 min-1) with target concentration (Tc) at 2.0-µg mL-1 were administered. When the predicted propofol concentration at the effect site (Es) reached half of Es value, Es was increased to previous Es + 1 µg mL-1, successively, until loss of consciousness. In rapid induction group (R), patients were induced with TCI of propofol with plasma (6.0 µg mL-1) at effect site, and waited until loss of consciousness. RESULTS: In rapid induction group, Tc for loss of consciousness was significantly lower compared to slow induction group (1.67 ± 0.76 and 2.50 ± 0.56 µg mL-1, respectively, p = 0.004). CONCLUSION: The predicted propofol concentration at the effect site for loss of consciousness is different for rapid induction and slow induction, even with the same pharmacokinetic model of propofol and the same balance constant between plasma and effect site. .

JUSTIFICATIVA E OBJETIVO: estudos mostraram que a taxa de infusão de propofol pode influenciar na concentração prevista de propofol no local de ação (Ce). O objetivo deste estudo foi avaliar a Ce prevista pelo modelo farmacocinético de Marsh (ke0 0,26 min-1) na perda da consciência durante indução rápida ou lenta. MÉTODO: participaram deste estudo 28 pacientes, divididos aleatoriamente em dois grupos iguais. No grupo indução lenta (L), foram induzidos com propofol em infusão alvo-controlada (IAC) plasmática, modelo farmacocinético de Marsh (ke0 0,26 min-1), com concentração alvo (Ca) em 2,0 µg.ml-1. Quando a concentração de propofol prevista no local de ação (Ce) atingia metade do valor da Ca, aumentava-se a Ca para Ca anterior + 1 µg.ml-1. Assim sucessivamente até o momento da perda da consciência do paciente. No grupo indução rápida (R), os pacientes foram induzidos com propofol em IAC plasmática com Ca em 6,0 µg.ml-1 e aguardava-se a perda da consciência do paciente. RESULTADOS: no grupo indução rápida, a Ce na perda da consciência foi significativamente mais baixa em relação ao grupo de indução lenta (1,67 ± 0,76 e 2,50 ± 0,56 µg.ml-1, respectivamente, p = 0,004). CONCLUSÃO: a concentração prevista de propofol no local de ação durante a perda da consciência é diferente numa indução rápida e numa indução lenta, até com o mesmo modelo farmacocinético de propofol e a mesma constante de equilíbrio entre o plasma e o local de ação. .

JUSTIFICACIÓN Y OBJETIVO: Varios estudios han demostrado que la tasa de infusión del propofol puede influir en la concentración prevista de propofol en la región de acción (Ce). El objetivo de este estudio fue evaluar la Ce prevista por el modelo farmacocinético de Marsh (ke0 0,26 min-1) en la pérdida de la consciencia durante inducción rápida o lenta. MÉTODO: Participaron en este estudio 28 pacientes, divididos aleatoriamente en 2 grupos iguales. En el grupo de inducción lenta, se administró una inducción de propofol en infusión objetivo-controlada plasmática, modelo farmacocinético de Marsh (ke0 0,26 min-1), con concentración objetivo (Ca) en 2µg/ml-1. Cuando la concentración de propofol prevista en la Ce alcanzaba la mitad del valor de la Ca, esta aumentaba a la Ca anterior +1 µg/ml-1. Así fue sucesivamente hasta el momento de la pérdida de la consciencia del paciente. En el grupo de inducción rápida, los pacientes recibieron inducción con propofol en infusión objetivo-controlada plasmática con Ca en 6 µg/ml-1 y se esperó hasta la pérdida de consciencia del paciente. RESULTADOS: En el grupo inducción rápida, la Ce en la pérdida de la consciencia fue significativamente más baja con relación al grupo de inducción lenta (1,67 ± 0,76 y 2,50 ± 0,56 µg/ml-1, respectivamente; p = 0,004). CONCLUSIÓN: La concentración prevista de propofol en la Ce durante la pérdida de la consciencia es diferente en una inducción rápida y en una inducción lenta, hasta con el mismo modelo farmacocinético de propofol y la misma constante de equilibrio entre el plasma y la región de acción. .

[Comparative study between fast and slow induction of propofol given by target-controlled infusion: expected propofol concentration at the effect site. Randomized controlled trial]. / Estudo comparativo entre indução rápida e lenta de propofol em infusão alvo-controlada: concentração de propofol prevista no local de ação. Ensaio clínico aleatório.

BACKGROUND AND OBJECTIVE: studies have shown that rate of propofol infusion may influence the predicted propofol concentration at the effect site (Es). The aim of this study was to evaluate the Es predicted by the Marsh pharmacokinetic model (ke0 0.26min(-1)) in loss of consciousness during fast or slow induction. METHOD: the study included 28 patients randomly divided into two equal groups. In slow induction group (S), target-controlled infusion (TCI) of propofol with plasma, Marsh pharmacokinetic model (ke0 0.26min(-1)) with target concentration (Tc) at 2.0-µg.mL(-1) were administered. When the predicted propofol concentration at the effect site (Es) reached half of Es value, Es was increased to previous Es + 1µg.mL(-1), successively, until loss of consciousness. In rapid induction group (R), patients were induced with TCI of propofol with plasma (6.0µg.ml(-1)) at Es, and waited until loss of consciousness. RESULTS: in rapid induction group, Tc for loss of consciousness was significantly lower compared to slow induction group (1.67±0.76 and 2.50±0.56µg.mL(-1), respectively, p=0.004). CONCLUSION: the predicted propofol concentration at the effect site for loss of consciousness is different for rapid induction and slow induction, even with the same pharmacokinetic model of propofol and the same balance constant between plasma and effect site.

Time course of neuronal death following endothelin-1 induced focal ischemia in rats.

BACKGROUND: Endothelin-1 (ET-1) induced focal ischemia is increasingly being used as a preclinical model of stroke. Here, we described for the first time, the time course of neuronal death and infarct evolution during the first 7 days following ischemia. NEW METHOD: We used hematoxylin and eosin (H&E) staining to evaluate infarct progression and Fluoro-Jade C (FJC) to quantify neuronal degeneration at 24, 48, 72h and 7 days after ET-1 injection to the forelimb motor cortex in Sprague-Dawley rats. RESULTS: We found that infarct volume and neuronal degeneration are maximal at 24h post-stroke. Neuronal degeneration is also significantly reduced within 7 days of stroke induction. COMPARISON WITH EXISTING METHOD: This study is the first to provide a direct evaluation of both infarct volume evolution and neuronal death time course following ET-1 induced focal ischemia in the forelimb motor cortex. CONCLUSION: This study describes the short-term time course of neuronal death and brain injury in the ET-1 stroke model, which provides a significant reference when determining the appropriate time to commence neuroprotective or recovery promoting strategies.