Purpose: Proximal humerus fractures account for 4-5% of all fractures in adults and affect females more than males. With the advent of special locking plates, the treatment trend has shifted more towards a surgical approach. These methods have produced good results but very high complications rates have been reported in the literature.
View Article and Find Full Text PDFAberrant cognitive network activity and cognitive deficits are established features of chronic pain. However, the nature of cognitive network alterations associated with chronic pain and their underlying mechanisms require elucidation. Here, we report that the claustrum, a subcortical nucleus implicated in cognitive network modulation, is activated by acute painful stimulation and pain-predictive cues in healthy participants.
View Article and Find Full Text PDFIntroduction: Transient osteoporosis of the hip (TOH) is a poorly recognized self-limiting clinical entity. Due to a lack of awareness among the clinicians, the condition is often misdiagnosed leading to inappropriate treatment, thereby lengthening the time to diagnosis (TTD). In this study, we analyze the delay in TTD of TOH using plain radiographs and present the optimal management strategy.
View Article and Find Full Text PDFGenerating animal models for individual patients within clinically-useful timeframes holds great potential toward enabling personalized medicine approaches for genetic epilepsies. The ability to rapidly incorporate patient-specific genomic variants into model animals recapitulating elements of the patient's clinical manifestations would enable applications ranging from validation and characterization of pathogenic variants to personalized models for tailoring pharmacotherapy to individual patients. Here, we demonstrate generation of an animal model of an individual epilepsy patient with an ultra-rare variant of the NMDA receptor subunit GRIN2A, without the need for germline transmission and breeding.
View Article and Find Full Text PDFAberrant cognitive network activity and cognitive deficits are established features of chronic pain. However, the nature of cognitive network alterations associated with chronic pain and their underlying mechanisms require elucidation. Here, we report that the claustrum, a subcortical nucleus implicated in cognitive network modulation, is activated by acute painful stimulation and pain-predictive cues in healthy participants.
View Article and Find Full Text PDFImpulsive choice has enduring trait-like characteristics and is defined by preference for small immediate rewards over larger delayed ones. Importantly, it is a determining factor in the development and persistence of substance use disorder (SUD). Emerging evidence from human and animal studies suggests frontal cortical regions exert influence over striatal reward processing areas during decision-making in impulsive choice or delay discounting (DD) tasks.
View Article and Find Full Text PDFThe dorsal striatum (DS) mediates the selection of actions for reward acquisition necessary for survival. Striatal pathology contributes to several neuropsychiatric conditions, including aberrant selection of actions for specific rewards in addiction. A major source of glutamate driving striatal activity is the rostral intralaminar nuclei (rILN) of the thalamus.
View Article and Find Full Text PDFParvalbumin-expressing dorsal striatal fast-spiking interneurons, comprising ∼1% of the total dorsal striatal neuronal population, are necessary for the expression of compulsive-like ethanol consumption mice. Fast-spiking interneurons are driven to fire by glutamatergic inputs derived primarily from the cortex. However, these neurons also receive substantial GABAergic input from two sources: the globus pallidus and the reticular nucleus of the thalamus.
View Article and Find Full Text PDFRegulation of RNA processing contributes profoundly to tissue development and physiology. Here, we report that serine-arginine-rich splicing factor 1 (SRSF1) is essential for hepatocyte function and survival. Although SRSF1 is mainly known for its many roles in mRNA metabolism, it is also crucial for maintaining genome stability.
View Article and Find Full Text PDFSpatially distant areas of the cerebral cortex coordinate their activity into networks that are integral to cognitive processing. A common structural motif of cortical networks is co-activation of frontal and posterior cortical regions. The neural circuit mechanisms underlying such widespread inter-areal cortical coordination are unclear.
View Article and Find Full Text PDFEarly hypotheses of claustrum function were fueled by neuroanatomical data and yielded suggestions that the claustrum is involved in processes ranging from salience detection to multisensory integration for perceptual binding. While these hypotheses spurred useful investigations, incompatibilities inherent in these views must be reconciled to further conceptualize claustrum function amid a wealth of new data. Here, we review the varied models of claustrum function and synthesize them with developments in the field to produce a novel functional model: network instantiation in cognitive control (NICC).
View Article and Find Full Text PDFInhibitory fast-spiking interneurons in the dorsal striatum regulate actions and action strategies, including habits. Fast-spiking interneurons are widely believed to synchronize their firing due to the electrical synapses formed between these neurons. However, neuronal modelling data suggest convergent cortical input may also drive synchrony in fast-spiking interneuron networks.
View Article and Find Full Text PDFClassic psychedelic drugs such as psilocybin and lysergic acid diethylamide (LSD) have recaptured the imagination of both science and popular culture, and may have efficacy in treating a wide range of psychiatric disorders. Human and animal studies of psychedelic drug action in the brain have demonstrated the involvement of the serotonin 2A (5-HT2A) receptor and the cerebral cortex in acute psychedelic drug action, but different models have evolved to try to explain the impact of 5-HT2A activation on neural systems. Two prominent models of psychedelic drug action (the cortico-striatal thalamo-cortical, or CSTC, model and relaxed beliefs under psychedelics, or REBUS, model) have emphasized the role of different subcortical structures as crucial in mediating psychedelic drug effects.
View Article and Find Full Text PDFMost viral pathogens causing epidemics and pandemics are zoonotic, emerging from wildlife reservoirs like SARS CoV2 causing the global Covid-19 pandemic, although animal origin of this virus remains a mystery. Cross-species transmission of pathogens from animals to humans is known as zoonosis. However, pathogens are also transmitted from humans to animals in regions where there is a close interaction between animals and humans by 'reverse transmission' (anthroponosis).
View Article and Find Full Text PDFInt J Neuropsychopharmacol
August 2021
Psychedelic substances produce unusual and compelling changes in conscious experience that have prompted some to propose that psychedelics may provide unique insights explaining the nature of consciousness. At present, psychedelics, like other current scientific tools and methods, seem unlikely to provide information relevant to the so-called "hard problem of consciousness," which involves explaining how first-person experience can emerge. However, psychedelics bear on multiple "easy problems of consciousness," which involve relations between subjectivity, brain function, and behavior.
View Article and Find Full Text PDFIn this issue of Neuron, Soria-Gomez et al. (2021) investigate whether activation of the type 1 cannabinoid receptor at specific subcellular locations within a single neural circuit produces multimodal behavior. Their results demonstrate that location matters: striatonigral mitochondrial CB1 drives catalepsy while striatonigral plasma membrane CB1 receptors enable antinociception.
View Article and Find Full Text PDFThe thalamic rostral intralaminar nuclei (rILN) are a contiguous band of neurons that include the central medial, paracentral, and central lateral nuclei. The rILN differ from both thalamic relay nuclei, such as the lateral geniculate nucleus, and caudal intralaminar nuclei, such as the parafascicular nucleus, in afferent and efferent connectivity as well as physiological and synaptic properties. rILN activity is associated with a range of neural functions and behaviors, including arousal, pain, executive function, and action control.
View Article and Find Full Text PDFNuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. Here, we report a previously unknown function for the hepatic FXR-SHP axis in controlling protein N-linked glycosylation. Transcriptome analysis in liver-specific Fxr-Shp double knockout (LDKO) livers revealed induction of genes encoding enzymes in the N-glycosylation pathway, including , , , and FXR activation suppressed , while Shp deletion induced and Increased percentages of core-fucosylated and triantennary glycan moieties were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes.
View Article and Find Full Text PDFThe chemical synapse is the principal form of contact between neurons of the central nervous system. These synapses are typically configured as presynaptic axon terminations onto postsynaptic dendrites or somata, giving rise to axo-dendritic and axo-somatic synapses, respectively. Beyond these common synapse configurations are less-studied, non-canonical synapse types that are prevalent throughout the brain and significantly contribute to neural circuit function.
View Article and Find Full Text PDFJ Plast Reconstr Aesthet Surg
January 2021
Introduction: This study evaluates COVID-19 related patient risk, when undergoing management within one of the largest specialist centres in Europe, which rapidly implemented national COVID-19 safety guidelines.
Method: A prospective cohort study was undertaken in all patients who underwent surgical (n = 1429) or non-operative (n = 191) management during the UK COVID-19 pandemic peak (April-May 2020); all were evaluated for 30-day COVID-19 related death. A representative sample of elective/trauma/burns patients (surgery group, n = 729) were selected and also sub-analysed within a controlled cohort study design.
Background & Aims: Liver diseases are caused by many factors, such as genetics, nutrition, and viruses. Therefore, it is important to delineate transcriptomic changes that occur in various liver diseases.
Methods: We performed high-throughput sequencing of mouse livers with diverse types of injuries, including cholestasis, diet-induced steatosis, and partial hepatectomy.
Neuropsychopharmacology
January 2021
Compulsive alcohol consumption is a core, treatment-resistant feature of alcohol use disorder. The dorsomedial and dorsolateral striatum support goal-directed and habitual action strategies, respectively. How ethanol targets dorsolateral striatum to drive compulsive consumption is poorly understood.
View Article and Find Full Text PDFThis study was conducted to come up with data on Y-STR markers for the population of Rajasthan comprising of the western arid region of India. Y-STR analysis is an established tool in forensic DNA casework and ancestry research. We analyzed 23 Y-STRs in randomly selected 310 unrelated individuals living within the geographical area of Rajasthan to establish parameters of forensic interest.
View Article and Find Full Text PDFBackground: To achieve goals, organisms are often faced with complex tasks that require enhanced control of cognitive faculties for optimal performance. However, the neural circuit mechanisms underlying this ability are unclear. The claustrum is proposed to mediate a variety of functions ranging from sensory binding to cognitive control of action, but direct functional assessments of this telencephalic nucleus are lacking.
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