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Methodist DeBakey Cardiovascular Journal 2023In patients undergoing elective cardiovascular and thoracic surgery, malnutrition and the deterioration of nutritional status are associated with negative outcomes.... (Review)
Review
In patients undergoing elective cardiovascular and thoracic surgery, malnutrition and the deterioration of nutritional status are associated with negative outcomes. Recognition of the contributory factors and the complications stemming from surgical stress is important for the prevention and management of these patients. We have reviewed the literature available and focused on the nutritional and metabolic aspects affecting surgical patients, with emphasis on the recommendations of enhanced recovery protocols. The implementation of enhanced recovery protocols and nutritional support guidelines focusing on the surgical patient as part of a multidisciplinary approach would improve the nutritional status of surgical patients at risk for negative outcomes.
Topics: Humans; Nutritional Status; Perioperative Care; Postoperative Complications; Nutritional Support; Malnutrition
PubMed: 37547903
DOI: 10.14797/mdcvj.1248 -
Bulletin of Mathematical Biology Dec 2023Phylogenetic networks are an extension of phylogenetic trees that allow for the representation of reticulate evolution events. One of the classes of networks that has...
Phylogenetic networks are an extension of phylogenetic trees that allow for the representation of reticulate evolution events. One of the classes of networks that has gained the attention of the scientific community over the last years is the class of orchard networks, that generalizes tree-child networks, one of the most studied classes of networks. In this paper we focus on the combinatorial and algorithmic problem of the generation of binary orchard networks, and also of binary tree-child networks. To this end, we use that these networks are defined as those that can be recovered by reversing a certain reduction process. Then, we show how to choose a "minimum" reduction process among all that can be applied to a network, and hence we get a unique representation of the network that, in fact, can be given in terms of sequences of pairs of integers, whose length is related to the number of leaves and reticulations of the network. Therefore, the generation of networks is reduced to the generation of such sequences of pairs. Our main result is a recursive method for the efficient generation of all minimum sequences, and hence of all orchard (or tree-child) networks with a given number of leaves and reticulations. An implementation in C of the algorithms described in this paper, along with some computational experiments, can be downloaded from the public repository https://github.com/gerardet46/OrchardGenerator . Using this implementation, we have computed the number of binary orchard networks with at most 6 leaves and 8 reticulations.
Topics: Humans; Phylogeny; Mathematical Concepts; Models, Biological; Algorithms; Plant Leaves
PubMed: 38117376
DOI: 10.1007/s11538-023-01239-z -
Tidsskrift For Den Norske Laegeforening... Nov 2023
Topics: Humans; Pons; Demyelinating Diseases
PubMed: 37987074
DOI: 10.4045/tidsskr.23.0479 -
International Journal of Molecular... May 2024This Special Issue focused on the importance of phytochemicals for their use in the prevention and treatment of cancer [...].
This Special Issue focused on the importance of phytochemicals for their use in the prevention and treatment of cancer [...].
Topics: Phytochemicals; Humans; Neoplasms; Animals; Antineoplastic Agents, Phytogenic
PubMed: 38791488
DOI: 10.3390/ijms25105450 -
Brain : a Journal of Neurology Feb 2024The spinocerebellar ataxias (SCAs) are a group of dominantly inherited neurodegenerative diseases, several of which are caused by CAG expansion mutations (SCAs 1, 2, 3,...
The spinocerebellar ataxias (SCAs) are a group of dominantly inherited neurodegenerative diseases, several of which are caused by CAG expansion mutations (SCAs 1, 2, 3, 6, 7 and 12) and more broadly belong to the large family of over 40 microsatellite expansion diseases. While dysregulation of alternative splicing is a well defined driver of disease pathogenesis across several microsatellite diseases, the contribution of alternative splicing in CAG expansion SCAs is poorly understood. Furthermore, despite extensive studies on differential gene expression, there remains a gap in our understanding of presymptomatic transcriptomic drivers of disease. We sought to address these knowledge gaps through a comprehensive study of 29 publicly available RNA-sequencing datasets. We identified that dysregulation of alternative splicing is widespread across CAG expansion mouse models of SCAs 1, 3 and 7. These changes were detected presymptomatically, persisted throughout disease progression, were repeat length-dependent, and were present in brain regions implicated in SCA pathogenesis including the cerebellum, pons and medulla. Across disease progression, changes in alternative splicing occurred in genes that function in pathways and processes known to be impaired in SCAs, such as ion channels, synaptic signalling, transcriptional regulation and the cytoskeleton. We validated several key alternative splicing events with known functional consequences, including Trpc3 exon 9 and Kcnma1 exon 23b, in the Atxn1154Q/2Q mouse model. Finally, we demonstrated that alternative splicing dysregulation is responsive to therapeutic intervention in CAG expansion SCAs with Atxn1 targeting antisense oligonucleotide rescuing key splicing events. Taken together, these data demonstrate that widespread presymptomatic dysregulation of alternative splicing in CAG expansion SCAs may contribute to disease onset, early neuronal dysfunction and may represent novel biomarkers across this devastating group of neurodegenerative disorders.
Topics: Animals; Mice; Alternative Splicing; Spinocerebellar Ataxias; Cerebellum; Mutation; Disease Progression; Trinucleotide Repeat Expansion; Olivopontocerebellar Atrophies
PubMed: 37776516
DOI: 10.1093/brain/awad329 -
The Journal of Neuroscience : the... Jul 2023The amygdala plays a key role in the processing of itch and pain signals as well as emotion. A previous study revealed that the central nucleus of the amygdala...
The amygdala plays a key role in the processing of itch and pain signals as well as emotion. A previous study revealed that the central nucleus of the amygdala (CeA)-parabrachial nucleus (PBN) pathway is involved in pain regulation. The same pathway might also control itch. To test this possibility, prodynorphin (Pdyn)-Cre mice were used to optogenetically manipulate Pdyn CeA-to-PBN projections. We found that optogenetic stimulation of Pdyn amygdala neurons or Pdyn CeA-to-PBN projections inhibited histamine-evoked and chloroquine-evoked scratching. The number of Fos-positive neurons in the PBN increased following intradermal injection of chloroquine. Optogenetic stimulation of Pdyn CeA-to-PBN projections suppressed the increase in Fos expression in the PBN. Optogenetic stimulation of Pdyn CeA-to-PBN projections increased thermal and mechanical thresholds without affecting anxiety-like behavior. These results highlight the importance of dynorphinergic projections from the central amygdala to the parabrachial nucleus in the regulation of itch signaling. The central nucleus of the amygdala (CeA)-parabrachial nucleus (PBN) pathway regulates pain signaling. Using prodynorphin (Pdyn)-cre mice, we investigated the role of Pdyn CeA-to-PBN projections in itch. Optogenetic stimulation of Pdyn CeA-to-PBN projections inhibited pruritogen-evoked scratching and neuronal activity (c-Fos expression) in the PBN. Together, dynorphinergic projections from the central amygdala to the parabrachial nucleus are important for regulating itch information.
Topics: Mice; Animals; Parabrachial Nucleus; Central Amygdaloid Nucleus; Pain; Neurons; Pruritus; Chloroquine
PubMed: 37399333
DOI: 10.1523/JNEUROSCI.0726-23.2023 -
Sleep Sep 2023Long-term use of sodium oxybate (SXB), (also called gamma-hydroxybutyrate [GHB]) attenuates the cataplexy and sleepiness of human narcolepsy. We had previously found...
Long-term use of sodium oxybate (SXB), (also called gamma-hydroxybutyrate [GHB]) attenuates the cataplexy and sleepiness of human narcolepsy. We had previously found that chronic opiate usage in humans and long-term opiate administration to mice significantly increased the number of detected hypocretin/orexin (Hcrt) neurons, decreased their size, and increased Hcrt level in the hypothalamus. We also found that opiates significantly decreased cataplexy in human narcoleptics as well as in narcoleptic mice and that cessation of locus coeruleus neuronal activity preceded and was tightly linked to cataplectic attacks in narcoleptic dogs. We tested the hypothesis that SXB produces changes similar to opiates and now report that chronic SXB administration significantly increased the size of Hcrt neurons, the reverse of what we had seen with opiates in humans and mice. Levels of Hcrt in the hypothalamus were nonsignificantly lower, in contrast to the significant increase in hypothalamic Hcrt level after opiates. SXB decreased tyrosine hydroxylase levels in the locus coeruleus, the major descending projection of the hypocretin system, also the reverse of what we saw with opioids. Therefore despite some similar effects on narcoleptic symptomatology, SXB does not produce anatomical changes similar to those elicited by opiates. Analysis of changes in other links in the cataplexy pathway might further illuminate SXB's mechanism of action on narcolepsy.
Topics: Humans; Mice; Animals; Dogs; Orexins; Sodium Oxybate; Cataplexy; Locus Coeruleus; Narcolepsy; Neurons; Opiate Alkaloids
PubMed: 37155728
DOI: 10.1093/sleep/zsad135 -
Nature Communications Mar 2024The "dorsal pons", or "dorsal pontine tegmentum" (dPnTg), is part of the brainstem. It is a complex, densely packed region whose nuclei are involved in regulating many...
The "dorsal pons", or "dorsal pontine tegmentum" (dPnTg), is part of the brainstem. It is a complex, densely packed region whose nuclei are involved in regulating many vital functions. Notable among them are the parabrachial nucleus, the Kölliker Fuse, the Barrington nucleus, the locus coeruleus, and the dorsal, laterodorsal, and ventral tegmental nuclei. In this study, we applied single-nucleus RNA-seq (snRNA-seq) to resolve neuronal subtypes based on their unique transcriptional profiles and then used multiplexed error robust fluorescence in situ hybridization (MERFISH) to map them spatially. We sampled ~1 million cells across the dPnTg and defined the spatial distribution of over 120 neuronal subtypes. Our analysis identified an unpredicted high transcriptional diversity in this region and pinpointed the unique marker genes of many neuronal subtypes. We also demonstrated that many neuronal subtypes are transcriptionally similar between humans and mice, enhancing this study's translational value. Finally, we developed a freely accessible, GPU and CPU-powered dashboard ( http://harvard.heavy.ai:6273/ ) that combines interactive visual analytics and hardware-accelerated SQL into a data science framework to allow the scientific community to query and gain insights into the data.
Topics: Humans; Animals; Mice; In Situ Hybridization, Fluorescence; Pontine Tegmentum; Brain Stem; Locus Coeruleus; Parabrachial Nucleus; Ascomycota
PubMed: 38438345
DOI: 10.1038/s41467-024-45907-7 -
Journal of Neuroinflammation Sep 2023Most current disease-modifying therapies approved for multiple sclerosis (MS) are immunomodulatory drugs that counteract the aberrant activity of the immune system....
BACKGROUND
Most current disease-modifying therapies approved for multiple sclerosis (MS) are immunomodulatory drugs that counteract the aberrant activity of the immune system. Hence, new pharmacological interventions that drive anti-inflammatory activity and neuroprotection would represent interesting alternative therapeutic approaches or complementary strategies to treat progressive forms of MS. There is evidence of reduced noradrenaline levels and alterations to locus coeruleus (LC) noradrenergic neurons in MS patients, as well as in animal models of this disease, potentially factors contributing to the pathophysiology. Drugs that enhance noradrenaline appear to have some beneficial effects in MS, suggesting their potential to dampen the underlying pathology and disease progression.
METHODS
Therefore, we explored the consequences of chronic LC noradrenergic neurons activation by chemogenetics in experimental autoimmune encephalomyelitis (EAE) mice, the most widely used experimental model of MS. LC activation from the onset or the peak of motor symptoms was explored as two different therapeutic approaches, assessing the motor and non-motor behavioral changes as EAE progresses, and studying demyelination, inflammation and glial activation in the spinal cord and cerebral cortex during the chronic phase of EAE.
RESULTS
LC activation from the onset of motor symptoms markedly alleviated the motor deficits in EAE mice, as well as their anxiety-like behavior and sickness, in conjunction with reduced demyelination and perivascular infiltration in the spinal cord and glial activation in the spinal cord and prefrontal cortex (PFC). When animals exhibited severe paralysis, LC activation produced a modest alleviation of EAE motor symptoms and it enhanced animal well-being, in association with an improvement of the EAE pathology at the spinal cord and PFC level. Interestingly, the reduced dopamine beta-hydroxylase expression associated with EAE in the spinal cord and PFC was reversed through chemogenetic LC activation.
CONCLUSION
Therefore, clear anti-inflammatory and neuroprotective effects were produced by the selective activation of LC noradrenergic neurons in EAE mice, having greater benefits when LC activation commenced earlier. Overall, these data suggest noradrenergic LC neurons may be targets to potentially alleviate some of the motor and non-motor symptoms in MS.
Topics: Animals; Mice; Multiple Sclerosis; Locus Coeruleus; Encephalomyelitis, Autoimmune, Experimental; Adrenergic Neurons; Norepinephrine
PubMed: 37658434
DOI: 10.1186/s12974-023-02865-z -
Clinical Neurophysiology : Official... Sep 2023Clinical, behavioural, and neurophysiological effects of cerebellar transcranial direct current stimulation (tDCS) are highly variable and difficult to predict. We aimed...
OBJECTIVE
Clinical, behavioural, and neurophysiological effects of cerebellar transcranial direct current stimulation (tDCS) are highly variable and difficult to predict. We aimed to examine associations between cerebellar tDCS-induced electric field strength, morphometric posterior fossa parameters, and skin-cerebellum distance. As a secondary objective, field characteristics were compared between cephalic and extracephalic electrode configurations.
METHODS
Electric field simulations of midline cerebellar tDCS (7 × 5 cm electrodes, current intensities of 2 mA) were performed on MRI-based head models from 37 healthy adults using buccinator, frontopolar, and lower neck reference electrodes. Average field strengths were determined in eight regions of interest (ROIs) covering the anterior and posterior vermis and cerebellar hemispheres. Besides skin-cerebellum distance, various angles were measured between posterior fossa structures. Multivariable linear regression models were used to identify predictors of field strength in different ROIs.
RESULTS
Skin-cerebellum distance and "pons angle" were independently associated with field strength in the anterior and posterior vermis. "Cerebellar angle" and skin-cerebellum distance affected field strength in anterior and posterior regions of the right cerebellar hemisphere. Field strengths in all examined cerebellar areas were highest in the frontopolar and lowest in the lower neck montage, while the opposite was found for field focality. The lower neck montage induced considerably less spreading toward anterior cerebellar regions compared with the buccinator and frontopolar montages, which resulted in a more evenly distributed field within the cerebellum.
CONCLUSION
In addition to skin-cerebellum distance, interindividual differences in posterior fossa morphometry, specifically pons and cerebellar angle, explain part of the variability in cerebellar tDCS-induced electric field strength. Furthermore, when targeting the midline cerebellum with tDCS, an extracephalic reference electrode is associated with lower field strengths and higher field focality than cephalic montages.
SIGNIFICANCE
This study identifies two novel subject-specific anatomical factors that partly determine cerebellar tDCS-induced electric field strength and reveals differences in field characteristics between electrode montages.
Topics: Adult; Humans; Transcranial Direct Current Stimulation; Cerebellum; Head; Electrodes
PubMed: 37499446
DOI: 10.1016/j.clinph.2023.06.019