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OBJECTIVES: To determine the prevalence of organ impairment in long COVID patients at 6 and 12 months after initial symptoms and to explore links to clinical presentation. DESIGN: Prospective cohort study. PARTICIPANTS: Individuals. METHODS: In individuals recovered from acute COVID-19, we assessed symptoms, health status, and multi-organ tissue characterisation and function. SETTING: Two non-acute healthcare settings (Oxford and London). Physiological and biochemical investigations were performed at baseline on all individuals, and those with organ impairment were reassessed. MAIN OUTCOME MEASURES: Primary outcome was prevalence of single- and multi-organ impairment at 6 and 12 months post COVID-19. RESULTS: A total of 536 individuals (mean age 45 years, 73% female, 89% white, 32% healthcare workers, 13% acute COVID-19 hospitalisation) completed baseline assessment (median: 6 months post COVID-19); 331 (62%) with organ impairment or incidental findings had follow-up, with reduced symptom burden from baseline (median number of symptoms 10 and 3, at 6 and 12 months, respectively). Extreme breathlessness (38% and 30%), cognitive dysfunction (48% and 38%) and poor health-related quality of life (EQ-5D-5L\u2009
\n \n\n \n \nThe temporal lobe is implicated in higher cognitive processes and is one of the regions that underwent substantial reorganization during primate evolution. Its functions are instantiated, in part, by the complex layout of its structural connections. Here, we identified low-dimensional representations of structural connectivity variations in human temporal cortex and explored their microstructural underpinnings and associations to macroscale function. We identified three eigenmodes which described gradients in structural connectivity. These gradients reflected inter-regional variations in cortical microstructure derived from quantitative magnetic resonance imaging and postmortem histology. Gradient-informed models accurately predicted macroscale measures of temporal lobe function. Furthermore, the identified gradients aligned closely with established measures of functional reconfiguration and areal expansion between macaques and humans, highlighting their potential role in shaping temporal lobe function throughout primate evolution. Findings were replicated in several datasets. Our results provide robust evidence for three axes of structural connectivity in human temporal cortex with consistent microstructural underpinnings and contributions to large-scale brain network function.
\n \n\n \n \nAbstractEvolutionary modifications of the temporo-parietal cortex are considered to be a critical adaptation of the human brain. Cortical adaptations, however, can affect different aspects of brain architecture, including areal expansion or changes in connectivity profiles. We propose to distinguishing different types of brain reorganization using a computational neuroanatomy approach. We investigate the extent to which between-species alignment based on cortical myelin can predict changes in connectivity patterns across macaque, chimpanzee and human. We show that expansion and relocation of brain areas are sufficient to predict terminations of several white matter tracts in temporo-parietal cortex, including the middle and superior longitudinal fasciculus, but not of the arcuate fasciculus. This demonstrates that the arcuate fasciculus underwent additional evolutionary modifications affecting the connectivity pattern of the temporal lobe. The presented approach can flexibly be extended to include other features of cortical organization and other species, allowing direct tests of comparative hypotheses of brain organization.
\n \n\n \n \nThis paper presents a deep learning system applied for detecting anomalies from respiratory sound recordings. Initially, our system begins with audio feature extraction using Gammatone and Continuous Wavelet transformation. This step aims to transform the respiratory sound input into a two-dimensional spectrogram where both spectral and temporal features are presented. Then, our proposed system integrates Inception-residual-based backbone models combined with multi-head attention and multi-objective loss to classify respiratory anomalies. Instead of applying a simple concatenation approach by combining results from various spectrograms, we propose a linear combination, which has the ability to regulate equally the contribution of each individual spectrogram throughout the training process. To evaluate the performance, we conducted experiments over the benchmark dataset of SPRSound (The Open-Source SJTU Paediatric Respiratory Sound) proposed by the IEEE BioCAS 2022 challenge. As regards the Score computed by an average between the average score and harmonic score, our proposed system gained significant improvements of 9.7%, 15.8%, 17.8%, and 16.1% in Task 1-1, Task 1-2, Task 2-1, and Task 2-2, respectively, compared to the challenge baseline system. Notably, we achieved the Top-1 performance in Task 2-1 and Task 2-2 with the highest Score of 74.5% and 53.9%, respectively.
\n \n\n \n \nHuman immunodeficiency virus 1 (HIV-1) causes major health burdens worldwide and still lacks curative therapies and vaccines. Circadian rhythms are endogenous daily oscillations that coordinate an organism's response to its environment and invading pathogens. Peripheral viral loads of HIV-1 infected patients show diurnal variation; however, the underlying mechanisms remain unknown. Here, we demonstrate a role for the cell-intrinsic clock to regulate rhythmic HIV-1 replication in circadian-synchronized systems. Silencing the circadian activator Bmal1 abolishes this phenotype, and we observe BMAL1 binding to the HIV-1 promoter. Importantly, we show differential binding of the nuclear receptors REV-ERB and ROR to the HIV-long terminal repeat at different circadian times, demonstrating a dynamic interplay in time-of-day regulation of HIV-1 transcription. Bioinformatic analysis shows circadian regulation of host factors that control HIV-1 replication, providing an additional mechanism for rhythmic viral replication. This study increases our understanding of the circadian regulation of HIV-1, which can ultimately inform new therapies.
\n \n\n \n \nHuman immunodeficiency virus type 1 (HIV-1) causes a major burden on global health, and eradication of latent virus infection is one of the biggest challenges in the field. The circadian clock is an endogenous timing system that oscillates with a ~24\u2009h period regulating multiple physiological processes and cellular functions, and we recently reported that the cell intrinsic clock regulates rhythmic HIV-1 replication. Salt inducible kinases (SIK) contribute to circadian regulatory networks, however, there is limited evidence for SIKs regulating HIV-1 infection. Here, we show that pharmacological inhibition of SIKs perturbed the cellular clock and reduced rhythmic HIV-1 replication in circadian synchronised cells. Further, SIK inhibitors or genetic silencing of Sik expression inhibited viral replication in primary cells and in a latency model, respectively. Overall, this study demonstrates a role for salt inducible kinases in regulating HIV-1 replication and latency reactivation, which can provide innovative routes to better understand and target latent HIV-1 infection.
\n \n\n \n \nBetz cells, named in honor of Volodymyr Betz (1834-1894), who described them as \"giant pyramids\" in the primary motor cortex of primates and other mammalian species, are layer V extratelencephalic projection (ETP) neurons that directly innervate \u03b1-motoneurons of the brainstem and spinal cord. Despite their large volume and circumferential dendritic architecture, to date, no single molecular criterion has been established that unequivocally distinguishes adult Betz cells from other layer V ETP neurons. In primates, transcriptional signatures suggest the presence of at least two ETP neuron clusters that contain mature Betz cells; these are characterized by an abundance of axon guidance and oxidative phosphorylation transcripts. How neurodevelopmental programs drive the distinct positional and morphological features of Betz cells in humans remains unknown. Betz cells display a distinct biphasic firing pattern involving early cessation of firing followed by delayed sustained acceleration in spike frequency and magnitude. Few cell type-specific transcripts and electrophysiological characteristics are conserved between rodent layer V ETP neurons of the motor cortex and primate Betz cells. This has implications for the modeling of disorders that affect the motor cortex in humans, such as amyotrophic lateral sclerosis (ALS). Perhaps vulnerability to ALS is linked to the evolution of neural networks for fine motor control reflected in the distinct morphomolecular architecture of the human motor cortex, including Betz cells. Here, we discuss histological, molecular, and functional data concerning the position of Betz cells in the emerging taxonomy of neurons across diverse species and their role in neurological disorders.
\n \n\n \n \nThis dataset contains raw data of the publication entitled 'Higher densities of T-lymphocytes in the subsynovial connective tissue of people with carpal tunnel syndrome' . the data is available as an excel file.
\n \n\n \n \nOur study evaluated the morphological and functional outcomes, and the side effects, of voretigene neparvovec (VN) gene therapy for RPE65-mediated inherited retinal dystrophies (IRDs) in 12 eyes (six patients) at the Oxford Eye Hospital with a mean follow-up duration of 8.2 (range 1\u201312) months. All patients reported a subjective vision improvement 1 month after gene therapy. Best-corrected visual acuity (BCVA) remained stable (baseline: 1.28 (\u00b10.71) vs. last follow-up: 1.46 (\u00b10.60); p = 0.25). Average white Full-Field Stimulus Testing (FST) showed a trend towards improvement (baseline: \u22124.41 (\u00b110.62) dB vs. last follow-up: \u221211.98 (\u00b113.83) dB; p = 0.18). No changes in central retinal thickness or macular volume were observed. The side effects included mild intraocular inflammation (two eyes) and cataracts (four eyes). Retinal atrophy occurred in 10 eyes (eight mild, two severe) but did not impact FST measurements during the follow-up period. Increased intraocular pressure (IOP) was noted in three patients (six eyes); four eyes (two patients) required glaucoma surgery. The overall safety and effectiveness of VN treatment in our cohort align with previous VN clinical trials, except for the higher occurrence of retinal atrophy and increased IOP in our cohort. This suggests that raised IOP and retinal atrophy may be more common than previously reported.
\n \n\n \n \nAbstractThis work aims to investigate how smoking exerts effect on the development of inflammatory bowel disease (IBD). A prospective cohort study and a Mendelian randomization study are first conducted to evaluate the association between smoking behaviors, smoking-related DNA methylation and the risks of Crohn\u2019s disease (CD) and ulcerative colitis (UC). We then perform both genome-wide methylation analysis and co-localization analysis to validate the observed associations. Compared to never smoking, current and previous smoking habits are associated with increased CD (P\u2009=\u20097.09\u2009\u00d7\u200910\u221210) and UC (P\u2009<\u20092\u2009\u00d7\u200910\u221216) risk, respectively. DNA methylation alteration at cg17742416 [DNMT3A] is linked to both CD (P\u2009=\u20097.30\u2009\u00d7\u200910\u22128) and UC (P\u2009=\u20091.04\u2009\u00d7\u200910\u22124) risk, while cg03599224 [LTA/TNF] is associated with CD risk (P\u2009=\u20091.91\u2009\u00d7\u200910\u22126), and cg14647125 [AHRR] and cg23916896 [AHRR] are linked to UC risk (P\u2009=\u20090.001 and 0.002, respectively). Our study identifies biological mechanisms and pathways involved in the effects of smoking on the pathogenesis of IBD.
\n \n\n \n \nIn Cognitive-Behavioural Therapy for Insomnia (CBT-I) Across the Life Span: Guidelines and Clinical Protocols for Health Professionals, a team of distinguished medical researchers delivers a comprehensive exploration of various treatment protocols used by health professionals treating patients with insomnia from several different populations. The included treatment protocols are written by members of the European Academy for Cognitive-Behaviour Treatment for Insomnia and reflect the most current practice and theoretical models. The editors have included contributions from leading scholars throughout Europe, as well as up-and-coming researchers with new and exciting data and conclusions to share with the community of health practitioners treating patients experiencing insomnia. In the book, readers will find discussions of the presentation of insomnia in different professional populations - including healthcare workers and shift workers - as well as the presence of common comorbidities. They'll also discover: A thorough introduction to the disorder of insomnia, as well as the use of cognitive-behavioural therapy in the treatment of insomnia patients Comprehensive explorations of the influence of the lifespan and professional factors on the presentation and impact of insomnia on paediatric and adult patients In-depth discussions of frequently occurring comorbidities, including affective disorders, mental disorders, somatic disorders and chronic pain Fulsome treatments of the emotional processes associated with insomnia, including acceptance and commitment therapy and mindfulness training Perfect for psychologists, psychiatrists, social workers and other clinicians engaged in the treatment of insomnia, Cognitive-Behavioural Therapy for Insomnia (CBT-I) Across the Life Span: Guidelines and Clinical Protocols for Health Professionals will also earn a place in the libraries of medical researchers with a professional interest in CBT, insomnia and other sleep disorders.
\n \n\n \n \nThe clinical picture of insomnia encompasses day- and night-time symptoms. Typical night-time complaints are prolonged sleep latency, increased frequency of awakenings, difficulties getting back to sleep and early morning awakening. Day-time sequelae encompass fatigue, tiredness, reduced attention, impaired cognition, irritability, nervousness, anxiety and mood swings, including dysphoric or even depressed mood. DSM-5 (Diagnostic and Statistical Manual of the American Psychiatric Association, 5th edition), ICSD-3 (International Classification of Sleep Disorders, 3rd edition) and ICD-11 (International Classification of Diseases, 11th edition) summarise this condition as Insomnia Disorder (ID). Epidemiological studies demonstrated that ID is an important risk factor for somatic and mental health. The prevalence of ID is higher in women than in men and increases with age. Apart from a clinical interview, questionnaires should be used for the evaluation of insomnia. The core instrument is a standardised 7-14 day sleep diary that includes questions on sleep-related and daytime symptoms. Actigraphy and polysomnography can be considered for a subgroup of patients presenting with therapy-refractory insomnia or suspected occult sleep disorders. A thorough medical and psychiatric evaluation is advisable to evaluate clinically relevant comorbidities. Present illness concepts range from genetic and neurobiological to cognitive-behavioral models, forming the basis for Cognitive Behavioural Therapy for insomnia (CBT-I) encompassing sleep hygiene and education, relaxation methods, stimulus control, sleep restriction and cognitive techniques to reduce nocturnal ruminations. Recently published guidelines agree that CBT- I should be the first line treatment for insomnia.
\n \n\n \n \nSTUDY OBJECTIVES: Preliminary evidence suggests that the risk of Long COVID is higher among people with pre-existing medical conditions. Based on its proven adjuvant role in immunity, habitual sleep duration may alter the risk for developing Long COVID. The objective of this study was to determine whether the odds of Long COVID are higher amongst those with pre-existing medical conditions, and whether the strength of this association varies by habitual sleep duration. METHODS: Using data from 13,461 respondents from 16 countries who participated in the 2021 survey based International COVID Sleep Study II (ICOSS II), we studied the associations between habitual sleep duration, pre-existing medical conditions, and Long COVID. RESULTS: Of 2,508 individuals who had COVID-19, 61% reported at least one Long COVID symptom. Multivariable logistic regression analysis showed that the risk of having Long COVID was 1.8-fold higher for average-length sleepers (6-9h/night) with pre-existing medical conditions compared to those without pre-existing medical conditions [aOR 1.84 (1.18-2.90), P=0.008]. The risk of Long COVID was 3-fold higher for short sleepers with pre-existing medical conditions [aOR 2.95 (1.04-8.4), P=0.043] and not significantly higher for long sleepers with pre-existing conditions [aOR 2.11 (0.93-4.77), P=0.073] compared to average-length sleepers without pre-existing conditions. CONCLUSIONS: Habitual short nighttime sleep duration exacerbated the risk of Long COVID in individuals with pre-existing conditions. Restoring nighttime sleep to average duration represents a potentially modifiable behavioral factor to lower the odds of Long COVID for at-risk patients.
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