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1.
Pediatr Pulmonol ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38958238

ABSTRACT

OBJECTIVES: To quantify the association of ambient air pollution (particulate matter, PM2.5) exposure with medically attended acute respiratory illness among infants with bronchopulmonary dysplasia (BPD). STUDY DESIGN: Single center, retrospective cohort study of preterm infants with BPD in Metropolitan Philadelphia. Multivariable logistic regression quantified associations of annual mean PM2.5 exposure (per µg/m3) at the census block group level with medically attended acute respiratory illness, defined as emergency department (ED) visits or hospital readmissions within a year after first hospital discharge adjusting for age at neonatal intensive care unit (NICU) discharge, year, sex, race, insurance, BPD severity, and census tract deprivation. As a secondary analysis, we examined whether BPD severity modified the associations. RESULTS: Of the 378 infants included in the analysis, 189 were non-Hispanic Black and 235 were publicly insured. Census block PM2.5 level was not significantly associated with medically attended acute respiratory illnesses, ED visits, or hospital readmissions in the full study cohort. We observed significant effect modification by BPD grade; each 1 µg/m3 higher annual PM2.5 exposure was medically attended acute respiratory illness (adjusted odds ratio [aOR] 1.65, 95% CI: 1.06-2.63) among infants with Grade 1 BPD but not among infants with grade 3 BPD (aOR 0.83, 95% CI: 0.47-1.48) (interaction p = .024). CONCLUSIONS: Cumulative PM2.5 exposure in the year after NICU discharge was not significantly associated with medically attended acute respiratory illness among infants with BPD. However, infants with Grade 1 BPD had significantly higher odds with higher exposures. If replicated, these findings could inform anticipatory guidance for families of these infants to avoid outdoor activities during high pollution days after NICU discharge.

2.
Obes Res Clin Pract ; 18(3): 195-200, 2024.
Article in English | MEDLINE | ID: mdl-38955573

ABSTRACT

INTRODUCTION: Revisional bariatric surgery (RBS) for insufficient weight loss/weight regain or metabolic relapse is increasing worldwide. There is currently no large multinational, prospective data on 30-day morbidity and mortality of RBS. In this study, we aimed to evaluate the 30-day morbidity and mortality of RBS at participating centres. METHODS: An international steering group was formed to oversee the study. The steering group members invited bariatric surgeons worldwide to participate in this study. Ethical approval was obtained at the lead centre. Data were collected prospectively on all consecutive RBS patients operated between 15th May 2021 to 31st December 2021. Revisions for complications were excluded. RESULTS: A total of 65 global centres submitted data on 750 patients. Sleeve gastrectomy (n = 369, 49.2 %) was the most common primary surgery for which revision was performed. Revisional procedures performed included Roux-en-Y gastric bypass (RYGB) in 41.1 % (n = 308) patients, One anastomosis gastric bypass (OAGB) in 19.3 % (n = 145), Sleeve Gastrectomy (SG) in 16.7 % (n = 125) and other procedures in 22.9 % (n = 172) patients. Indications for revision included weight regain in 615(81.8 %) patients, inadequate weight loss in 127(16.9 %), inadequate diabetes control in 47(6.3 %) and diabetes relapse in 27(3.6 %). 30-day complications were seen in 80(10.7 %) patients. Forty-nine (6.5 %) complications were Clavien Dindo grade 3 or higher. Two patients (0.3 %) died within 30 days of RBS. CONCLUSION: RBS for insufficient weight loss/weight regain or metabolic relapse is associated with 10.7 % morbidity and 0.3 % mortality. Sleeve gastrectomy is the most common primary procedure to undergo revisional bariatric surgery, while Roux-en-Y gastric bypass is the most commonly performed revision.


Subject(s)
Bariatric Surgery , Reoperation , Weight Loss , Humans , Female , Male , Reoperation/statistics & numerical data , Bariatric Surgery/methods , Bariatric Surgery/mortality , Bariatric Surgery/adverse effects , Middle Aged , Adult , Prospective Studies , Postoperative Complications/mortality , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Obesity, Morbid/surgery , Obesity, Morbid/mortality , Gastric Bypass/methods , Gastric Bypass/mortality , Gastric Bypass/adverse effects , Gastrectomy/methods , Gastrectomy/adverse effects , Weight Gain , Morbidity
3.
Biomed Opt Express ; 15(5): 3265-3284, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38855664

ABSTRACT

It has been known for more than 220 years that the image quality of the human eye is significantly degraded by chromatic aberrations. Recently, it was shown experimentally that correcting chromatic aberrations results in a 0.2- to 0.8-line improvement in visual acuity. Here we ask, is this expected? We developed tools that enable simulations of the optical impact of physiologically relevant amounts of chromatic aberration in real human eyes and combined these with tools that compute the visual acuity of an ideal observer. This allows us to characterize the theoretical impact of chromatic aberration correction on visual acuity. Results indicate a substantive improvement of 0.4- to 2-lines in ideal observer visual acuity with chromatic aberration correction. Ideal observer thresholds benefit significantly more from correction of longitudinal than correction of transverse chromatic aberration. Finally, improvements in ideal observer visual acuity are greater for subjects with less monochromatic aberration, such that subjects with better baseline optical quality benefit most from correction of chromatic aberrations.

4.
Nanoscale ; 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38922329

ABSTRACT

Electron-assisted oxidation of Co-Si-based focused electron beam induced deposition (FEBID) materials is shown to form a 2-4 nm metal oxide surface layer on top of an electrically insulating silicon oxide layer less than 10 nm thick. Differences between thermal and electron-induced oxidation on the resulting microstructure are illustrated.

5.
Article in English | MEDLINE | ID: mdl-38791862

ABSTRACT

OBJECTIVE: To analyze the association of components of the Centers for Disease Control and Prevention (CDC) Environmental Justice Index (EJI) with respiratory health outcomes among infants with bronchopulmonary dysplasia (BPD) within one year after discharge from the neonatal intensive care unit. METHODS: This was a retrospective cohort study of a cohort of preterm infants with BPD. Multivariable logistic regression models estimated associations of EJI and its components with medically attended acute respiratory illness, defined as an ED visit or inpatient readmission, within one year of discharge from the neonatal intensive care unit. A mediation analysis was conducted to evaluate how environmental injustice may contribute to racial disparities in acute respiratory illness. RESULTS: Greater EJI was associated with an increased risk of medically attended respiratory illness (per EJI standard deviation increment, aOR 1.38, 95% CI: 1.12-1.69). Of the index's components, the Environmental Burden Module's Air pollution domain had the greatest association (aOR 1.44, 95% CI: 1.44-2.61). With respect to individual indicators within the EJI, Diesel Particulate Matter (DSLPM) and Air Toxic Cancer Risk (ATCR) demonstrated the strongest relationship (aOR 2.06, 95% CI: 1.57-2.71 and aOR 2.10, 95% CI: 1.59-2.78, respectively). Among non-Hispanic Black infants, 63% experienced a medically attended acute respiratory illness as compared to 18% of non-Hispanic White infants. DSLPM mediated 39% of the Black-White disparity in medically attended acute respiratory illness (p = 0.004). CONCLUSIONS: Environmental exposures, particularly air pollution, are associated with post-discharge respiratory health outcomes among preterm infants with BPD after adjusting for clinical, demographic, and social vulnerability risk factors. Certain types of air pollutants, namely, DSLPM, are more greatly associated with acute respiratory illness. Environmental exposures may contribute to racial disparities in medically attended acute respiratory illness among infants with BPD.


Subject(s)
Bronchopulmonary Dysplasia , Infant, Premature , Humans , Bronchopulmonary Dysplasia/epidemiology , Retrospective Studies , Infant, Newborn , Male , Female , Environmental Exposure/adverse effects , Patient Discharge/statistics & numerical data , Respiratory Tract Diseases/epidemiology , Air Pollution/adverse effects , United States/epidemiology , Infant
6.
Nat Commun ; 15(1): 4235, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38762489

ABSTRACT

Inflammation induced by lung infection is a double-edged sword, moderating both anti-viral and immune pathogenesis effects; the mechanism of the latter is not fully understood. Previous studies suggest the vasculature is involved in tissue injury. Here, we report that expression of Sparcl1, a secreted matricellular protein, is upregulated in pulmonary capillary endothelial cells (EC) during influenza-induced lung injury. Endothelial overexpression of SPARCL1 promotes detrimental lung inflammation, with SPARCL1 inducing 'M1-like' macrophages and related pro-inflammatory cytokines, while SPARCL1 deletion alleviates these effects. Mechanistically, SPARCL1 functions through TLR4 on macrophages in vitro, while TLR4 inhibition in vivo ameliorates excessive inflammation caused by endothelial Sparcl1 overexpression. Finally, SPARCL1 expression is increased in lung ECs from COVID-19 patients when compared with healthy donors, while fatal COVID-19 correlates with higher circulating SPARCL1 protein levels in the plasma. Our results thus implicate SPARCL1 as a potential prognosis biomarker for deadly COVID-19 pneumonia and as a therapeutic target for taming hyperinflammation in pneumonia.


Subject(s)
COVID-19 , Endothelial Cells , Lung , Macrophage Activation , SARS-CoV-2 , Animals , Humans , COVID-19/immunology , COVID-19/virology , COVID-19/metabolism , COVID-19/pathology , Mice , Endothelial Cells/metabolism , Endothelial Cells/virology , Endothelial Cells/immunology , SARS-CoV-2/physiology , Lung/virology , Lung/pathology , Lung/immunology , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 4/genetics , Calcium-Binding Proteins/metabolism , Calcium-Binding Proteins/genetics , Mice, Inbred C57BL , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Pneumonia, Viral/metabolism , Male , Macrophages/metabolism , Macrophages/immunology , Female , Mice, Knockout , Extracellular Matrix Proteins
7.
Inorg Chem ; 63(18): 8131-8141, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38639743

ABSTRACT

Mixed metal oxyhalides are an exciting class of photocatalysts, capable of the sustainable generation of fuels and remediation of pollutants with solar energy. Bismuth oxyhalides of the types Bi4MO8X (M = Nb and Ta; X = Cl and Br) and Bi2AO4X (A = most lanthanides; X = Cl, Br, and I) have an electronic structure that imparts photostability, as their valence band maxima (VBM) are composed of O 2p orbitals rather than X np orbitals that typify many other bismuth oxyhalides. Here, flux-based synthesis of intergrowth Bi4NbO8Cl-Bi2GdO4Cl is reported, testing the hypothesis that both intergrowth stoichiometry and M identity serve as levers toward tunable optoelectronic properties. X-ray scattering and atomically resolved electron microscopy verify intergrowth formation. Facile manipulation of the Bi4NbO8Cl-to-Bi2GdO4Cl ratio is achieved with the specific ratio influencing both the crystal and electronic structures of the intergrowths. This compositional flexibility and crystal structure engineering can be leveraged for photocatalytic applications, with comparisons to the previously reported Bi4TaO8Cl-Bi2GdO4Cl intergrowth revealing how subtle structural and compositional features can impact photocatalytic materials.

8.
Sensors (Basel) ; 24(7)2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38610473

ABSTRACT

The integration of machine learning and robotics brings promising potential to tackle the application challenges of mobile robot navigation in industries. The real-world environment is highly dynamic and unpredictable, with increasing necessities for efficiency and safety. This demands a multi-faceted approach that combines advanced sensing, robust obstacle detection, and avoidance mechanisms for an effective robot navigation experience. While hybrid methods with default robot operating system (ROS) navigation stack have demonstrated significant results, their performance in real time and highly dynamic environments remains a challenge. These environments are characterized by continuously changing conditions, which can impact the precision of obstacle detection systems and efficient avoidance control decision-making processes. In response to these challenges, this paper presents a novel solution that combines a rapidly exploring random tree (RRT)-integrated ROS navigation stack and a pre-trained YOLOv7 object detection model to enhance the capability of the developed work on the NAV-YOLO system. The proposed approach leveraged the high accuracy of YOLOv7 obstacle detection and the efficient path-planning capabilities of RRT and dynamic windows approach (DWA) to improve the navigation performance of mobile robots in real-world complex and dynamically changing settings. Extensive simulation and real-world robot platform experiments were conducted to evaluate the efficiency of the proposed solution. The result demonstrated a high-level obstacle avoidance capability, ensuring the safety and efficiency of mobile robot navigation operations in aviation environments.

9.
J Oral Rehabil ; 51(7): 1109-1112, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38475861

ABSTRACT

OBJECTIVE: The objective of this commentary is to advocate for a holistic, ontology-based definition of bruxism. The intention is to synthesise the best aspects of current definitions into a structured ontological model, thereby refining and enhancing a comprehensive understanding of the full spectrum of bruxism. MATERIALS AND METHODS: The commentary elaborates on the process of integrating these insights into a hierarchical ontology that aligns with ontological principles. SETTINGS AND SAMPLE POPULATION: Not directly applicable as this is a commentary. RESULTS/CONCLUSION: The proposed ontology-based definition of bruxism aims to clarify communication within the medical community and advance research by enabling a comprehensive ontology-based classification of bruxism. By aligning with ontological principles, this approach aspires to act as a catalyst for further research, discussion and consensus in the field.


Subject(s)
Bruxism , Semantics , Terminology as Topic , Humans , Biological Ontologies , Holistic Health
10.
Phys Rev Lett ; 132(9): 094002, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38489623

ABSTRACT

We study the statistics of velocity circulation in two-dimensional classical and quantum turbulence. We perform numerical simulations of the incompressible Navier-Stokes and the Gross-Pitaevskii (GP) equations for the direct and inverse cascades. Our GP simulations display clear energy spectra compatible with the double cascade theory of two-dimensional classical turbulence. In the inverse cascade, we found that circulation intermittency in quantum turbulence is the same as in classical turbulence. We compare GP data to Navier-Stokes simulations and experimental data from Zhu et al. [Phys. Rev. Lett. 130, 214001 (2023)PRLTAO0031-900710.1103/PhysRevLett.130.214001]. In the direct cascade, for nearly incompressible GP flows, classical and quantum turbulence circulation displays the same self-similar scaling. When compressibility becomes important, quasishocks generate quantum vortices and the equivalence of quantum and classical turbulence only holds for low-order moments. Our results establish the boundaries of the equivalence between two-dimensional classical and quantum turbulence.

11.
Phys Rev Lett ; 132(9): 093801, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38489636

ABSTRACT

We report the first experimental demonstration of the replica symmetry breaking (RSB) phenomenon in a fiber laser system supporting standard mode-locking (SML) regime. Though theoretically predicted, this photonic glassy phase remained experimentally undisclosed so far. We employ an ytterbium-based mode-locked fiber laser with a very rich phase diagram. Two phase transitions are observed separating three different regimes: cw, quasi-mode-locking (QML), and SML. The regimes are intrinsically related to the distinct dynamics of intensity fluctuations in the laser spectra. We set the connection between the RSB glassy phase with frustrated modes and onset of L-shaped intensity distributions in the QML regime, which impact directly the replica overlap measure.

12.
Nanoscale Adv ; 6(7): 1837-1846, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38545290

ABSTRACT

The 16e square-planar bis-thiolato-Au(iii) complexes [AuIII(1,2-dicarba-closo-dodecarborane-1,2-dithiolato)2][NBu4] (Au-1) and [AuIII(4-methyl-1,2-benzenedithiolato)2][NBu4] (Au-2) have been synthesized and fully characterized. Au-1 and Au-2 were encapsulated in the symmetrical triblock copolymer poloxamer (Pluronic®) P123 containing blocks of poly(ethylene oxide) and poly(propylene oxide), giving micelles AuMs-1 and AuMs-2. High electron flux in scanning transmission electron microscopy (STEM) was used to generate single gold atoms and gold nanocrystals on B/S-doped graphitic surfaces, or S-doped amorphous carbon surfaces from AuMs-1 and AuMs-2, respectively. Electron energy loss spectroscopy (EELS) data suggested strong interactions of gold atoms/nanocrystals with boron in the B/S-doped graphitic matrix. Density-functional theory (DFT) calculations, also supported the experimental findings, pointing towards strong Au-B bonds, depending on the charge on the Au-(B-graphene) fragment and the presence of further defects in the graphene lattice.

13.
Sensors (Basel) ; 24(5)2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38474913

ABSTRACT

The field of learning-based navigation for mobile robots is experiencing a surge of interest from research and industry sectors. The application of this technology for visual aircraft inspection tasks within a maintenance, repair, and overhaul (MRO) hangar necessitates efficient perception and obstacle avoidance capabilities to ensure a reliable navigation experience. The present reliance on manual labour, static processes, and outdated technologies limits operation efficiency in the inherently dynamic and increasingly complex nature of the real-world hangar environment. The challenging environment limits the practical application of conventional methods and real-time adaptability to changes. In response to these challenges, recent years research efforts have witnessed advancement with machine learning integration aimed at enhancing navigational capability in both static and dynamic scenarios. However, most of these studies have not been specific to the MRO hangar environment, but related challenges have been addressed, and applicable solutions have been developed. This paper provides a comprehensive review of learning-based strategies with an emphasis on advancements in deep learning, object detection, and the integration of multiple approaches to create hybrid systems. The review delineates the application of learning-based methodologies to real-time navigational tasks, encompassing environment perception, obstacle detection, avoidance, and path planning through the use of vision-based sensors. The concluding section addresses the prevailing challenges and prospective development directions in this domain.

14.
J Phys Chem C Nanomater Interfaces ; 128(7): 2967-2977, 2024 Feb 22.
Article in English | MEDLINE | ID: mdl-38444783

ABSTRACT

The investigation of precursor classes for the fabrication of nanostructures is of specific interest for maskless fabrication and direct nanoprinting. In this study, the differences in material composition depending on the employed process are illustrated for focused-ion-beam- and focused-electron-beam-induced deposition (FIBID/FEBID) and compared to the thermal decomposition in chemical vapor deposition (CVD). This article reports on specific differences in the deposit composition and microstructure when the (H3Si)2Fe(CO)4 precursor is converted into an inorganic material. Maximum metal/metalloid contents of up to 90 at. % are obtained in FIBID deposits and higher than 90 at. % in CVD films, while FEBID with the same precursor provides material containing less than 45 at. % total metal/metalloid content. Moreover, the Fe:Si ratio is retained well in FEBID and CVD processes, but FIBID using Ga+ ions liberates more than 50% of the initial Si provided by the precursor. This suggests that precursors for FIBID processes targeting binary materials should include multiple bonding such as bridging positions for nonmetals. In addition, an in situ method for investigations of supporting thermal effects of precursor fragmentation during the direct-writing processes is presented, and the applicability of the precursor for nanoscale 3D FEBID writing is demonstrated.

15.
Elife ; 122024 Feb 14.
Article in English | MEDLINE | ID: mdl-38354040

ABSTRACT

Neurostimulation of the hippocampal formation has shown promising results for modulating memory but the underlying mechanisms remain unclear. In particular, the effects on hippocampal theta-nested gamma oscillations and theta phase reset, which are both crucial for memory processes, are unknown. Moreover, these effects cannot be investigated using current computational models, which consider theta oscillations with a fixed amplitude and phase velocity. Here, we developed a novel computational model that includes the medial septum, represented as a set of abstract Kuramoto oscillators producing a dynamical theta rhythm with phase reset, and the hippocampal formation, composed of biophysically realistic neurons and able to generate theta-nested gamma oscillations under theta drive. We showed that, for theta inputs just below the threshold to induce self-sustained theta-nested gamma oscillations, a single stimulation pulse could switch the network behavior from non-oscillatory to a state producing sustained oscillations. Next, we demonstrated that, for a weaker theta input, pulse train stimulation at the theta frequency could transiently restore seemingly physiological oscillations. Importantly, the presence of phase reset influenced whether these two effects depended on the phase at which stimulation onset was delivered, which has practical implications for designing neurostimulation protocols that are triggered by the phase of ongoing theta oscillations. This novel model opens new avenues for studying the effects of neurostimulation on the hippocampal formation. Furthermore, our hybrid approach that combines different levels of abstraction could be extended in future work to other neural circuits that produce dynamical brain rhythms.


Subject(s)
Brain , Gastropoda , Animals , Heart Rate , Hippocampus , Computer Simulation
17.
Nat Commun ; 15(1): 43, 2024 01 02.
Article in English | MEDLINE | ID: mdl-38167811

ABSTRACT

Inhibition of epigenetic regulators by small molecules is an attractive strategy for cancer treatment. Recently, we characterised the role of lysine methyltransferase 9 (KMT9) in prostate, lung, and colon cancer. Our observation that the enzymatic activity was required for tumour cell proliferation identified KMT9 as a potential therapeutic target. Here, we report the development of a potent and selective KMT9 inhibitor (compound 4, KMI169) with cellular activity through structure-based drug design. KMI169 functions as a bi-substrate inhibitor targeting the SAM and substrate binding pockets of KMT9 and exhibits high potency, selectivity, and cellular target engagement. KMT9 inhibition selectively downregulates target genes involved in cell cycle regulation and impairs proliferation of tumours cells including castration- and enzalutamide-resistant prostate cancer cells. KMI169 represents a valuable tool to probe cellular KMT9 functions and paves the way for the development of clinical candidate inhibitors as therapeutic options to treat malignancies such as therapy-resistant prostate cancer.


Subject(s)
Prostatic Neoplasms, Castration-Resistant , Prostatic Neoplasms , Male , Humans , Methyltransferases , Cell Line, Tumor , Cell Proliferation , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/genetics , Prostatic Neoplasms, Castration-Resistant/genetics , Nitriles/therapeutic use
18.
Curr Opin Neurobiol ; 84: 102814, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38016260

ABSTRACT

Just over a decade ago, a novel GABAergic input originating from a subpopulation of external globus pallidus neurons known as Arkypallidal and projecting exclusively to the striatum was unveiled. At the single-cell level, these pallidostriatal Arkypallidal projections represent one of the largest extrinsic sources of GABA known to innervate the dorsal striatum. This discovery has sparked new questions regarding their role in striatal information processing, the circuit that recruit these neurons, and their influence on behaviour, especially in the context of action selection vs. inhibition. In this review, we will present the different anatomo-functional organization of Arkypallidal neurons as compared to classic Prototypic neurons, including their unique molecular properties and what is known about their specific input/output synaptic organization. We will further describe recent findings that demonstrate one mode of action of Arkypallidal neurons, which is to convey feedback inhibition to the striatum, and how this mechanism is differentially modulated by both striatal projection pathways. Lastly, we will delve into speculations on their mechanistic contribution to striatal action execution or inhibition.


Subject(s)
Basal Ganglia , Globus Pallidus , Globus Pallidus/metabolism , Neurons/physiology , Corpus Striatum , Neural Pathways/metabolism
19.
J Neurosci ; 44(9)2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38123981

ABSTRACT

Excessive oscillatory activity across basal ganglia (BG) nuclei in the ß frequencies (12-30 Hz) is a hallmark of Parkinson's disease (PD). While the link between oscillations and symptoms remains debated, exaggerated ß oscillations constitute an important biomarker for therapeutic effectiveness in PD. The neuronal mechanisms of ß-oscillation generation however remain unknown. Many existing models rely on a central role of the subthalamic nucleus (STN) or cortical inputs to BG. Contrarily, neural recordings and optogenetic manipulations in normal and parkinsonian rats recently highlighted the central role of the external pallidum (GPe) in abnormal ß oscillations, while showing that the integrity of STN or motor cortex is not required. Here, we evaluate the mechanisms for the generation of abnormal ß oscillations in a BG network model where neuronal and synaptic time constants, connectivity, and firing rate distributions are strongly constrained by experimental data. Guided by a mean-field approach, we show in a spiking neural network that several BG sub-circuits can drive oscillations. Strong recurrent STN-GPe connections or collateral intra-GPe connections drive γ oscillations (>40 Hz), whereas strong pallidostriatal loops drive low-ß (10-15 Hz) oscillations. We show that pathophysiological strengthening of striatal and pallidal synapses following dopamine depletion leads to the emergence of synchronized oscillatory activity in the mid-ß range with spike-phase relationships between BG neuronal populations in-line with experiments. Furthermore, inhibition of GPe, contrary to STN, abolishes oscillations. Our modeling study uncovers the neural mechanisms underlying PD ß oscillations and may thereby guide the future development of therapeutic strategies.


Subject(s)
Parkinson Disease , Subthalamic Nucleus , Rats , Animals , Basal Ganglia/physiology , Globus Pallidus/physiology , Neurons/physiology , Beta Rhythm/physiology
20.
Geroscience ; 46(2): 2681-2695, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38141157

ABSTRACT

The increasing aging of the human population is currently and for the coming decades a major public health issue in many countries, requiring the implementation of global public health policies promoting healthy and successful aging. Individuals are not equal in the face of aging and some can present exceptional healthspan and/or lifespan, which are notably influenced by both genetic and environmental factors. Research and studies on human aging, healthy aging and longevity should rely in particular on cohorts of long-lived individuals, also including biological samples allowing studies on the biology of aging and longevity. In this manuscript, we provide for the first time a complete description of the CEPH (Centre d'Etude du Polymophisme Humain) Aging cohort, an exceptional cohort recruited during the 90s to 2000s, including more than 1700 French long-lived individuals (≥ 90 years old) born between 1875 and 1916 as well as for some of them their siblings and offspring. Among the participants, 1265 were centenarians, including 255 semi-supercentenarians ([105-110] years old) and 25 supercentenarians (≥ 110 years old). The available anthropometric, epidemiologic and clinical data for the cohort participants are described and especially the collection of blood-derived biological samples associated with the cohort which includes DNA, cryopreserved cells and cell lines, plasma, and serum. This biological collection from the first cohort of centenarians in the world is an inestimable resource for ongoing and future molecular, cellular, and functional studies aimed at deciphering the mechanisms of human (successful) aging and longevity.


Subject(s)
Biological Specimen Banks , Longevity , Aged, 80 and over , Humans , Longevity/genetics , Aging/genetics , Longitudinal Studies , Health Status
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