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The Lancet. Neurology Oct 2022Prospective epidemiological studies in industrial societies indicate that 7 h of sleep per night in people aged 18 years or older is optimum, with higher and lower... (Review)
Review
Prospective epidemiological studies in industrial societies indicate that 7 h of sleep per night in people aged 18 years or older is optimum, with higher and lower amounts of sleep predicting a shorter lifespan. Humans living a hunter-gatherer lifestyle (eg, tribal groups) sleep for 6-8 h per night, with the longest sleep durations in winter. The prevalence of insomnia in hunter-gatherer populations is low (around 2%) compared with the prevalence of insomnia in industrial societies (around 10-30%). Sleep deprivation studies, which are done to gain insights into sleep function, are often confounded by the effects of stress. Consideration of the duration of spontaneous daily sleep across species of mammals, which ranges from 2 h to 20 h, can provide important insights into sleep function without the stress of deprivation. Sleep duration is not related to brain size or cognitive ability. Rather, sleep duration across species is associated with their ecological niche and feeding requirements, indicating a role for wake-sleep balance in food acquisition and energy conservation. Brain temperature drops from waking levels during non-rapid eye movement (non-REM) sleep and rises during REM sleep. Average daily REM sleep time of homeotherm orders is negatively correlated with average body and brain temperature, with the largest amount of REM sleep in egg laying (monotreme) mammals, moderate amounts in pouched (marsupial) mammals, lower amounts in placental mammals, and the lowest amounts in birds. REM sleep might, therefore, have a key role in the regulation of temperature and metabolism of the brain during sleep and in the facilitation of alert awakening.
Topics: Animals; Female; Humans; Mammals; Placenta; Pregnancy; Prospective Studies; Sleep; Sleep Initiation and Maintenance Disorders
PubMed: 36115365
DOI: 10.1016/S1474-4422(22)00210-1 -
Frontiers in Pharmacology 2021A program to identify novel intravenous sedatives with a short and predictable duration of action was initiated in the late 1990's by Glaxo Wellcome. The program... (Review)
Review
A program to identify novel intravenous sedatives with a short and predictable duration of action was initiated in the late 1990's by Glaxo Wellcome. The program focussed on the identification of ester-based benzodiazepine derivatives that are rapidly broken down by esterases. Remimazolam was identified as one of the lead compounds. The project at Glaxo was shelved for strategic reasons at the late lead optimization stage. Via the GSK ventures initiative, the program was acquired by the small biotechnology company, TheraSci, and, through successive acquisitions, developed as the besylate salt at CeNeS and PAION. The development of remimazolam besylate has been slow by industry standards, primarily because of the resource limitations of these small companies. It has, however, recently been approved for anesthesia in Japan and South Korea, procedural sedation in the United States, China, and Europe, and for compassionate use in intensive care unit sedation in Belgium. A second development program of remimazolam was later initiated in China, using a slightly different salt form, remimazolam tosylate. This salt form of the compound has also recently been approved for procedural sedation in China. Remimazolam has the pharmacological profile of a classical benzodiazepine, such as midazolam, but is differentiated from other intravenous benzodiazepines by its rapid conversion to an inactive metabolite resulting in a short onset/offset profile. It is differentiated from other intravenous hypnotic agents, such as propofol, by its low liability for cardiovascular depression, respiratory depression, and injection pain. The benzodiazepine antagonist flumazenil can reverse the effects of remimazolam in case of adverse events and further shorten recovery times. The aim of this review is to provide an analysis of, and perspective on, published non-clinical and clinical information on 1) the pharmacology, metabolism, pharmacokinetics, and pharmacodynamic profile of remimazolam, 2) the profile of remimazolam compared with established agents, 3) gaps in the current understanding of remimazolam, 4) the compound's discovery and development process and 5) likely future developments in the clinical use of remimazolam.
PubMed: 34354587
DOI: 10.3389/fphar.2021.690875 -
Critical Care (London, England) May 2023The optimal treatment duration and the nature of regimen of antibiotics (monotherapy or combination therapy) for Pseudomonas aeruginosa ventilator‑associated pneumonia... (Randomized Controlled Trial)
Randomized Controlled Trial
Association between combination antibiotic therapy as opposed as monotherapy and outcomes of ICU patients with Pseudomonas aeruginosa ventilator-associated pneumonia: an ancillary study of the iDIAPASON trial.
BACKGROUND
The optimal treatment duration and the nature of regimen of antibiotics (monotherapy or combination therapy) for Pseudomonas aeruginosa ventilator‑associated pneumonia (PA-VAP) remain debated. The aim of this study was to evaluate whether a combination antibiotic therapy is superior to a monotherapy in patients with PA-VAP in terms of reduction in recurrence and death, based on the 186 patients included in the iDIAPASON trial, a multicenter, randomized controlled trial comparing 8 versus 15 days of antibiotic therapy for PA-VAP.
METHODS
Patients with PA-VAP randomized in the iDIAPASON trial (short-duration-8 days vs. long-duration-15 days) and who received appropriate antibiotic therapy were eligible in the present study. The main objective is to compare mortality at day 90 according to the antibiotic therapy received by the patient: monotherapy versus combination therapy. The primary outcome was the mortality rate at day 90. The primary outcome was compared between groups using a Chi-square test. Time from appropriate antibiotic therapy to death in ICU or to censure at day 90 was represented using Kaplan-Meier survival curves and compared between groups using a Log-rank test.
RESULTS
A total of 169 patients were included in the analysis. The median duration of appropriate antibiotic therapy was 14 days. At day 90, among 37 patients (21.9%) who died, 17 received monotherapy and 20 received a combination therapy (P = 0.180). Monotherapy and combination antibiotic therapy were similar for the recurrence rate of VAP, the number of extra pulmonary infections, or the acquisition of multidrug-resistant (MDR) bacteria during the ICU stay. Patients in combination therapy were exposed to mechanical ventilation for 28 ± 12 days, as compared with 23 ± 11 days for those receiving monotherapy (P = 0.0243). Results remain similar after adjustment for randomization arm of iDIAPASON trial and SOFA score at ICU admission.
CONCLUSIONS
Except longer durations of antibiotic therapy and mechanical ventilation, potentially related to increased difficulty in achieving clinical cure, the patients in the combination therapy group had similar outcomes to those in the monotherapy group.
TRIAL REGISTRATION
NCT02634411 , Registered 15 December 2015.
Topics: Humans; Anti-Bacterial Agents; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Respiration, Artificial; Intensive Care Units
PubMed: 37254209
DOI: 10.1186/s13054-023-04457-y -
Frontiers in Immunology 2023Sleep enhances the antibody response to vaccination, but the relationship between sleep and mRNA vaccination against severe acute respiratory syndrome coronavirus 2... (Observational Study)
Observational Study
INTRODUCTION
Sleep enhances the antibody response to vaccination, but the relationship between sleep and mRNA vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not fully understood.
METHODS
In this prospective observational study, we investigated the influence of sleep habits on immune acquisition induced by mRNA vaccines against SARS-CoV-2 in 48 healthy adults (BNT-162b2, n=34; mRNA-1273, n=14; female, n=30, 62.5%; male, n=18, 37.5%; median age, 39.5 years; interquartile range, 33.0-44.0 years) from June 2021 to January 2022. The study measured sleep duration using actigraphy and sleep diaries, which covered the periods of the initial and booster vaccinations.
RESULTS
Multivariable linear regression analysis showed that actigraphy-measured objective sleep duration 3 and 7 days after the booster vaccination was independently and significantly correlated with higher antibody titers (B=0.003; 95% confidence interval, 0.000-0.005; Beta=0.337; p=0.02), even after controlling for covariates, including age, sex, the type of vaccine, and reactogenicity to the vaccination. Associations between acquired antibody titer and average objective sleep duration before vaccination, and any period of subjective sleep duration measured by sleep diary were negligible.
DISCUSSION
Longer objective, but not subjective, sleep duration after booster vaccination enhances antibody response. Hence, encouraging citizens to sleep longer after mRNA vaccination, especially after a booster dose, may increase protection against SARS-CoV-2.
STUDY REGISTRATION
This study is registered at the University Hospital Medical Information Network Center (UMIN: https://www.umin.ac.jp) on July 30, 2021, #UMIN000045009.
Topics: Adult; Female; Humans; Male; COVID-19; COVID-19 Vaccines; Sleep Duration; Vaccination; Antibody Formation; Antibodies, Viral; mRNA Vaccines; Immunization, Secondary
PubMed: 38149250
DOI: 10.3389/fimmu.2023.1242302 -
Psychopharmacology Nov 2022Exercise participation remains low despite clear benefits. Rats engage in voluntary wheel running (VWR) that follows distinct phases of acquisition, during which VWR...
RATIONALE
Exercise participation remains low despite clear benefits. Rats engage in voluntary wheel running (VWR) that follows distinct phases of acquisition, during which VWR escalates, and maintenance, during which VWR remains stable. Understanding mechanisms driving acquisition and maintenance of VWR could lead to novel strategies to promote exercise. The two phases of VWR resemble those that occur during operant conditioning and, therefore, might involve similar neural substrates. The dorsomedial (DMS) dorsal striatum (DS) supports the acquisition of operant conditioning, whereas the dorsolateral striatum (DLS) supports its maintenance.
OBJECTIVES
Here we sought to characterize the roles of DS subregions in VWR. Females escalate VWR and operant conditioning faster than males. Thus, we also assessed for sex differences.
METHODS
To determine the causal role of DS subregions in VWR, we pharmacologically inactivated the DMS or DLS of adult, male and female, Long-Evans rats during the two phases of VWR. The involvement of DA receptor 1 (D1)-expressing neurons in the DS was investigated by quantifying cfos mRNA within this neuronal population.
RESULTS
We observed that, in males, the DMS and DLS are critical for VWR exclusively during acquisition and maintenance, respectively. In females, the DMS is also critical only during acquisition, but the DLS contributes to VWR during both VWR phases. DLS D1 neurons could be an important driver of VWR escalation during acquisition.
CONCLUSIONS
The acquisition and maintenance of VWR involve unique neural substrates in the DS that vary by sex. Results reveal targets for sex-specific strategies to promote exercise.
Topics: Rats; Animals; Female; Male; Rats, Long-Evans; Motor Activity; Corpus Striatum; Neostriatum; RNA, Messenger
PubMed: 36195731
DOI: 10.1007/s00213-022-06243-0 -
Nature Methods Oct 2022A common goal of fluorescence microscopy is to collect data on specific biological events. Yet, the event-specific content that can be collected from a sample is...
A common goal of fluorescence microscopy is to collect data on specific biological events. Yet, the event-specific content that can be collected from a sample is limited, especially for rare or stochastic processes. This is due in part to photobleaching and phototoxicity, which constrain imaging speed and duration. We developed an event-driven acquisition framework, in which neural-network-based recognition of specific biological events triggers real-time control in an instant structured illumination microscope. Our setup adapts acquisitions on-the-fly by switching between a slow imaging rate while detecting the onset of events, and a fast imaging rate during their progression. Thus, we capture mitochondrial and bacterial divisions at imaging rates that match their dynamic timescales, while extending overall imaging durations. Because event-driven acquisition allows the microscope to respond specifically to complex biological events, it acquires data enriched in relevant content.
Topics: Biological Assay; Microscopy, Fluorescence; Mitochondria; Photobleaching
PubMed: 36076039
DOI: 10.1038/s41592-022-01589-x -
Frontiers in Neurology 2019Many clinical applications based on deep learning and pertaining to radiology have been proposed and studied in radiology for classification, risk assessment,... (Review)
Review
Many clinical applications based on deep learning and pertaining to radiology have been proposed and studied in radiology for classification, risk assessment, segmentation tasks, diagnosis, prognosis, and even prediction of therapy responses. There are many other innovative applications of AI in various technical aspects of medical imaging, particularly applied to the acquisition of images, ranging from removing image artifacts, normalizing/harmonizing images, improving image quality, lowering radiation and contrast dose, and shortening the duration of imaging studies. This article will address this topic and will seek to present an overview of deep learning applied to neuroimaging techniques.
PubMed: 31474928
DOI: 10.3389/fneur.2019.00869 -
Biochemical Pharmacology Nov 2023Breast cancer stands as the most prevalent and heterogeneous malignancy affecting women globally, posing a substantial health concern. Enhanced comprehension of tumor... (Review)
Review
Breast cancer stands as the most prevalent and heterogeneous malignancy affecting women globally, posing a substantial health concern. Enhanced comprehension of tumor pathology and the development of novel therapeutics are pivotal for advancing breast cancer treatment. Contemporary breast cancer investigation heavily leans on in vivo models and conventional cell culture techniques. Nonetheless, these approaches often encounter high failure rates in clinical trials due to species disparities and tissue structure variations. To address this, three-dimensional cultivation of organoids, resembling organ-like structures, has emerged as a promising alternative. Organoids represent innovative in vitro models that mirror in vivo tissue microenvironments. They retain the original tumor's diversity and facilitate the expansion of tumor samples from diverse origins, facilitating the representation of varying tumor stages. Optimized breast cancer organoid models, under precise culture conditions, offer benefits including convenient sample acquisition, abbreviated cultivation durations, and genetic stability. These attributes ensure a faithful replication of in vivo traits of breast cancer cells. As intricate cellular entities boasting spatial arrangements, breast cancer organoid models harbor substantial potential in precision medicine, organ transplantation, modeling intricate diseases, gene therapy, and drug innovation. This review delivers an overview of organoid culture techniques and outlines future prospects for organoid modeling.
Topics: Humans; Female; Breast Neoplasms; Drug Evaluation, Preclinical; Early Detection of Cancer; Organoids; Tumor Microenvironment
PubMed: 37709150
DOI: 10.1016/j.bcp.2023.115803 -
Sports Medicine - Open Dec 2022The goal-directed decision-making process of effort distribution (i.e. pacing) allows individuals to efficiently use energy resources as well as to manage the impact of...
BACKGROUND
The goal-directed decision-making process of effort distribution (i.e. pacing) allows individuals to efficiently use energy resources as well as to manage the impact of fatigue on performance during exercise. Given the shared characteristics between pacing behaviour and other skilled behaviour, it was hypothesized that pacing behaviour would adhere to the same processes associated with skill acquisition and development.
METHODS
PubMed, Web of Science and PsycINFO databases between January 1995 and January 2022 were searched for articles relating to the pacing behaviour of individuals (1) younger than 18 years of age, or (2) repeatedly performing the same exercise task, or (3) with different levels of experience.
RESULTS
The search resulted in 64 articles reporting on the effect of age (n = 33), repeated task exposure (n = 29) or differing levels of experience (n = 13) on pacing behaviour. Empirical evidence identifies the development of pacing behaviour starts during childhood (~ 10 years old) and continues throughout adolescence. This development is characterized by an increasingly better fit to the task demands, encompassing the task characteristics (e.g. duration) and environment factors (e.g. opponents). Gaining task experience leads to an increased capability to attain a predetermined pace and results in pacing behaviour that better fits task demands.
CONCLUSIONS
Similar to skilled behaviour, physical maturation and cognitive development likely drive the development of pacing behaviour. Pacing behaviour follows established processes of skill acquisition, as repeated task execution improves the match between stimuli (e.g. task demands and afferent signals) and actions (i.e. continuing, increasing or decreasing the exerted effort) with the resulting exercise task performance. Furthermore, with increased task experience attentional capacity is freed for secondary tasks (e.g. incorporating opponents) and the goal selection is changed from achieving task completion to optimizing task performance. As the development and acquisition of pacing resemble that of other skills, established concepts in the literature (e.g. intervention-induced variability and augmented feedback) could enrich pacing research and be the basis for practical applications in physical education, healthcare, and sports.
PubMed: 36484867
DOI: 10.1186/s40798-022-00540-w -
NPJ Science of Learning Sep 2023We investigated the influence of the time-of-day and sleep on skill acquisition (i.e., skill improvement immediately after a training-session) and consolidation (i.e.,...
We investigated the influence of the time-of-day and sleep on skill acquisition (i.e., skill improvement immediately after a training-session) and consolidation (i.e., skill retention after a time interval including sleep). Three groups were trained at 10 a.m. (G10), 3 p.m. (G3), or 8 p.m. (G8) on a finger-tapping task. We recorded the skill (i.e., the ratio between movement duration and accuracy) before and immediately after the training to evaluate acquisition, and after 24 h to measure consolidation. We did not observe any difference in acquisition according to the time of the day. Interestingly, we found a performance improvement 24 h after the evening training (G8), while the morning (G10) and the afternoon (G3) groups deteriorated and stabilized their performance, respectively. Furthermore, two control experiments (G8 and G8) supported the idea that a night of sleep contributes to the skill consolidation of the evening group. These results show a consolidation when the training is carried out in the evening, close to sleep, and forgetting when the training is carried out in the morning, away from sleep. This finding may have an important impact on the planning of training programs in sports, clinical, or experimental domains.
PubMed: 37658041
DOI: 10.1038/s41539-023-00176-9