ABSTRACT
Topological materials have been recently regarded as ideal catalysts for heterogeneous reactions due to their surface metallic states and high carrier mobility. However, the underlying relationship between their catalytic performance and topological states is under debate. It has been discovered that the electride 12CaO·7Al2 O3 (C12A7:4e- ) hosts multifold fermions and Fermi arcs on the (001) surface near the Fermi level due to the interstitial electrons. Through the comparison of catalytic performance under different doping and strain conditions, based on the hydrogen evolution process, it has been demonstrated that the excellent catalytic performance indeed originates from topological properties. A linear relationship between the length of Fermi arcs, and Gibbs free energy (ΔGH* ) has been found, which not only provides the direct evidence to link the enhanced catalytic performance and surface Fermi arc states, but also fully clarifies the fundamental mechanism in topological catalysis.
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Linking clinical services to community-based resources is a promising strategy for assisting patients with chronic disease prevention and management. However, there remains a gap in understanding how to effectively develop and implement community-clinical linkages (CCLs), especially in communities of color. The Healthy Here initiative used Stage Theory of organizational change to implement a centralized wellness referral system, linking primary care clinics to community organizations in majority Hispanic/Latinx and Native American communities. Data were collected using a standardized referral form. Facilitators and challenges were identified through semi-structured discussions with partner organizations. Between 2016 and 2021, 43 clinics and 497 health care providers made 7,465 referrals, the majority of which were from the focus populations. The average proportion of patients referred by clinic champions decreased significantly over time, reflecting diffusion of the intervention within clinics. Facilitators to system success included building on existing networked partnerships, utilizing a centralized referral center, leveraging funding, sharing data, addressing challenges collectively, incorporating multilevel leadership, and co-developing and testing a standardized referral form and process with a single clinic and provider before scaling up. Challenges included funding restrictions, decreasing referrals within clinics over time, changing availability of resources and programs, and the COVID-19 pandemic. This innovative initiative demonstrates that CCLs can be developed and implemented to successfully reach Hispanic/Latinx and Native American communities and provides strategies for overcoming challenges.
Subject(s)
COVID-19 , Pandemics , Humans , Referral and Consultation , Chronic Disease , Delivery of Health CareABSTRACT
PURPOSE: Multi-detector computed tomography (MDCT) is superior in fracture detection than conventional radiography; however, dose is increased. Cone-beam computed tomography (CBCT) offers higher spatial resolution and lower dose than MDCT. Manufacturers offer an ultra-low-dose algorithm. This study compares the diagnostic accuracy of the ultra-low-dose CBCT (ULDCBCT) with that of the standard-dose CBCT (SDCBCT). MATERIALS AND METHODS: In total, 64 patients were scanned with both the SDCBCT and the ULDCBCT protocols. Both studies were reported by two consultant radiologists with fellowship training in emergency radiology separated in time. The reporter recorded a diagnosis of fracture or normal and diagnostic confidence using a 5-point Likert scale. The gold standard was taken as the SDCBCT. Reporters were blinded to the indication and the SDCBCT report. Cases of discrepancy were resolved by consensus. RESULTS: There were 34 fractures and 30 cases had no fracture. Several fractures were missed using the UDCBCT, and there were also several cases of overdiagnosis. ULD was inferior to SD for fracture diagnosis (p < 0.00001). The diagnostic accuracy of ULDCBCT was 82.8% (75.1-88.9 CI). The diagnostic accuracy of plain radiograph was 64% (55.1-75.7% CI). Diagnostic confidence was reduced; the mean confidence for SDCBCT was 4.68 vs 4.12 for ULDCBCT (p < 0.001). The Kappa for interobserver agreement was 0.6. CONCLUSION: ULDCBCT is inferior to SDCBCT in fracture detection and confidence is reduced. For diagnostic studies, the standard dose should be used.
Subject(s)
Fractures, Bone , Radiology , Cone-Beam Computed Tomography , Fractures, Bone/diagnostic imaging , Humans , Multidetector Computed Tomography , RadiographyABSTRACT
We investigate the cause of spatial superexchange anisotropy in a family of copper-based, quasi-two-dimensional materials with very similar geometries. The compounds in this family differ mainly in their inter-layer separation but they have very different magnetic interactions, even within the basal plane. We use density functional theory and Wannier functions to parameterize two complimentary tight-binding models and show that the superexchange between the Cu2+ ions is dominated by a σ-mediated interaction between hybrid Cu-pyrazine orbitals centered on the copper atoms. We find no correlations between the strength of this exchange interaction and homologous geometric features across the compounds, such as Cu and pyrazine bond lengths and orientations of nearby counterions. We find that the pyrazine tilt angles do not affect the Cu-pyrazine-Cu exchange because the lowest unoccupied molecular orbital on pyrazine is at a very high energy (relative to the frontier orbitals, which are Cu-based). We conclude that careful control of the entire crystal structure, including non-homologous geometric features such as the inter-layer organic ligands, is vital for engineering magnetic properties.
ABSTRACT
BACKGROUND: MicroRNAs (miRNAs), important regulators of gene expression, have been implicated in a variety of disorders. The expression pattern of miRNAs in paediatric atopic dermatitis (AD) has not been well studied. OBJECTIVES: We sought to investigate miRNA expression profiles in different blood compartments of infants with AD. METHODS: Small RNA and analysis with the HTG EdgeSeq system were performed to identify differentially expressed miRNAs in peripheral blood mononuclear cells (PBMCs) and plasma of infants with AD vs. age-matched healthy controls, with reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) used for validation and measurement of miRNA targets. Logistic regression models with area under the receiving operating characteristic estimation was used to evaluate the diagnostic potential of chosen miRNAs for AD. RESULTS: RNA sequencing was performed to access miRNA expression profiles in paediatric AD. We identified 10 differentially expressed miRNAs in PBMCs and eight dysregulated miRNAs in plasma of infants with AD compared with controls. Upregulated miRNAs in PBMCs included miRNAs known to be involved in inflammation: miR-223-3p, miR-126-5p and miR-143-3p. Differential expression of only one miRNA, miR-451a, was observed in both PBMCs and plasma of children with AD. Dysregulation of three miRNAs (miR-451a, miR-143-3p and miR-223-3p) was validated in larger numbers of samples and miR-451a was identified as a predictive biomarker for the early diagnosis of the disease. Experimentally verified targets of miR-451a, interleukin 6 receptor (IL6R) and proteasome subunit beta type-8 (PSMB8), were increased in patients with AD, negatively correlated with miR-451a levels and upregulated following inhibition of miR-451a in PBMCs. CONCLUSIONS: In infants with AD, a distinct peripheral blood miRNA signature is seen, highlighting the systemic effects of the disease. miR-451a is uniquely expressed in different blood compartments of patients with AD and may serve as a promising novel biomarker for the early diagnosis of AD.
Subject(s)
Dermatitis, Atopic , MicroRNAs , Child , Dermatitis, Atopic/genetics , Gene Expression Profiling , Humans , Infant , Leukocytes, Mononuclear , MicroRNAs/genetics , Real-Time Polymerase Chain ReactionABSTRACT
Introducción: La cateterización venosa central es un procedimiento usual en Unidades de Cuidados Intensivos (UCI). El ultrasonido (US) para guiar la cateterización, ofrece ventajas, permitiendo tener una imagen topográfica precisa del vaso, reduciendo las complicaciones, el tiempo y el número de punciones. Objetivo: determinar, si la US en la colocación de catéteres venosos centrales (CVC), podría disminuir el número de punciones y lograr la cateterización exitosa. Población y métodos: Estudio descriptivo, prospectivo de los CVC colocados mediante punción guiada por US, en una UCI polivalente del Hospital de Pediatría Juan P. Garrahan, entre el año 2018 al 2019. Población: pacientes de 1 mes a 18 años que requirieron colocación de un CVS por US. Se consideró significativo un valor de p< 0.05. Resultados: VYI en 66 pacientes (43,5%), VF fue en 86 pacientes (56,5%). 86 (56,5%) CVC, fueron insertados en el primer intento y 66 (43,5%), requirieron más de un intento. Las inserciones en VYI fueron exitosas en el primer intento en 46 pac. (53,5%) 20 pac. requirieron más de un intento (30,3%) p 0,004 OR 0,37 (IC 95% 0,18-0,78. En <6 meses los CVC colocados en VYI tuvieron menos riesgo de requerir más de un intento, con respecto a aquellos en los cuales se eligió la VF, p 0,0026 OR 0,31 (IC 95% 0,12 -0,75). 5,2% presentaron complicaciones, no hubo mortalidad relacionada al procedimiento. Conclusiones: La inserción de CVC guiados por US fue segura y significativamente exitosa en el primer intento cuando el vaso de elección fue la VYI, especialmente en < 6 meses (AU)
IIntroduction: Central venous catheterization is a common procedure in intensive care units (ICU). The use of ultrasound (US) to guide catheterization offers advantages, allowing for an accurate topographic image of the vessel, reducing complications as well as time and number of punctures. Objective: To determine whether the use of US for the placement of central venous catheters (CVCs) may decrease the number of punctures and achieve successful catheterization. Patients and methods: A descriptive, prospective study was conducted of CVCs placed by US-guided puncture at a general ICU of Hospital de Pediatría Juan P. Garrahan between 2018 and 2019. Patients from 1 month to 18 years of age who required US-guided placement of a CVC were included. A p< 0.05 was considered significant. Results: The internal jugular vein (IJV) was used in 66 (43.5%) and the femoral vein (FV) in 86 patients (56.5%). Overall, in 86 (56.5%) CVC were inserted on the first attempt and 66 (43.5%) required more than one attempt. Insertions into the VYI were successful on the first attempt in 46 (53.5%) patients and 20 (30.3%) patients required more than one attempt, p 0.004; OR 0.37 (95% CI 0.18-0.78). In patients <6 months CVCs placed in the IJV had a lower risk of requiring more than one attempt compared to those in which the FV was chosen, p 0.0026 OR 0.31 (95% CI 0.12 -0.75). Complications occurred in 5.2%; no procedure-related mortality was observed. Conclusions: US-guided insertion of CVC was safe and significantly successful on the first attempt when the vessel of choice was the IJV, especially in patients < 6 months (AU)
Subject(s)
Humans , Infant , Child, Preschool , Child , Adolescent , Catheterization, Central Venous/adverse effects , Catheterization, Central Venous/methods , Intensive Care Units, Pediatric , Ultrasonography, Interventional/instrumentation , Ultrasonography, Interventional/methods , Central Venous Catheters , Prospective Studies , Femoral Vein , Jugular VeinsABSTRACT
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
ABSTRACT
The islet in type 2 diabetes (T2D) is characterized by amyloid deposits derived from islet amyloid polypeptide (IAPP), a protein co-expressed with insulin by ß-cells. In common with amyloidogenic proteins implicated in neurodegeneration, human IAPP (hIAPP) forms membrane permeant toxic oligomers implicated in misfolded protein stress. Here, we establish that hIAPP misfolded protein stress activates HIF1α/PFKFB3 signaling, this increases glycolysis disengaged from oxidative phosphorylation with mitochondrial fragmentation and perinuclear clustering, considered a protective posture against increased cytosolic Ca2+ characteristic of toxic oligomer stress. In contrast to tissues with the capacity to regenerate, ß-cells in adult humans are minimally replicative, and therefore fail to execute the second pro-regenerative phase of the HIF1α/PFKFB3 injury pathway. Instead, ß-cells in T2D remain trapped in the pro-survival first phase of the HIF1α injury repair response with metabolism and the mitochondrial network adapted to slow the rate of cell attrition at the expense of ß-cell function.
Subject(s)
Diabetes Mellitus, Type 2/pathology , Endoplasmic Reticulum Stress/physiology , Insulin-Secreting Cells/pathology , Islet Amyloid Polypeptide/metabolism , Unfolded Protein Response/physiology , Adult , Animals , Animals, Genetically Modified , Apoptosis , Cell Line, Tumor , Diabetes Mellitus, Type 2/metabolism , Disease Models, Animal , Glycolysis/physiology , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Islet Amyloid Polypeptide/genetics , Male , Middle Aged , Mitophagy/physiology , Oxidative Phosphorylation , Phosphofructokinase-2/metabolism , Protein Aggregates/physiology , RatsABSTRACT
In this report, we describe an innovative bolstering technique that resulted in successful skin graft take to the floor of the mouth when the teeth and alveolus were unavailable for anchorage.
Subject(s)
Mouth/surgery , Skin Transplantation/methods , Alveolar Process/surgery , Humans , Mouth Mucosa/surgery , Suture Techniques , Tooth/surgeryABSTRACT
This corrects the article DOI: 10.1103/PhysRevLett.119.087204.
ABSTRACT
We show that the anisotropy of the effective spin model for the dimer Mott insulator phase of κ-(BEDT-TTF)_{2}X salts is dramatically different from that of the underlying tight-binding model. Intradimer quantum interference results in a model of coupled spin chains, where frustrated interchain interactions suppress long-range magnetic order. Thus, we argue, the "spin liquid" phase observed in some of these materials is a remnant of the Tomonaga-Luttinger physics of a single chain. This is consistent with previous experiments and resolves some outstanding puzzles.
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Cell replication is a fundamental attribute of growth and repair in multicellular organisms. Pancreatic beta-cells in adults rarely enter cell cycle, hindering the capacity for regeneration in diabetes. Efforts to drive beta-cells into cell cycle have so far largely focused on regulatory molecules such as cyclins and cyclin-dependent kinases (CDKs). Investigations in cancer biology have uncovered that adaptive changes in metabolism, the mitochondrial network, and cellular Ca2+ are critical for permitting cells to progress through the cell cycle. Here, we investigated these parameters in the replication-competent beta-cell line INS 832/13. Cell cycle synchronization of this line permitted evaluation of cell metabolism, mitochondrial network, and cellular Ca2+ compartmentalization at key cell cycle stages. The mitochondrial network is interconnected and filamentous at G1/S but fragments during the S and G2/M phases, presumably to permit sorting to daughter cells. Pyruvate anaplerosis peaks at G1/S, consistent with generation of biomass for daughter cells, whereas mitochondrial Ca2+ and respiration increase during S and G2/M, consistent with increased energy requirements for DNA and lipid synthesis. This synchronization approach may be of value to investigators performing live cell imaging of Ca2+ or mitochondrial dynamics commonly undertaken in INS cell lines because without synchrony widely disparate data from cell to cell would be expected depending on position within cell cycle. Our findings also offer insight into why replicating beta-cells are relatively nonfunctional secreting insulin in response to glucose. They also provide guidance on metabolic requirements of beta-cells for the transition through the cell cycle that may complement the efforts currently restricted to manipulating cell cycle to drive beta-cells through cell cycle.
Subject(s)
Cell Cycle/physiology , Insulin-Secreting Cells/metabolism , Mitochondria/metabolism , Mitochondrial Dynamics/physiology , Animals , Cell Division/physiology , Cell Line , Cyclin-Dependent Kinases/metabolism , Cyclins/metabolism , DNA Replication/genetics , Mitochondria/genetics , RatsABSTRACT
Attention-deficit hyperactivity disorder (ADHD) is a prevalent and highly heritable disorder of childhood with negative lifetime outcomes. Although candidate gene and genome-wide association studies have identified promising common variant signals, these explain only a fraction of the heritability of ADHD. The observation that rare structural variants confer substantial risk to psychiatric disorders suggests that rare variants might explain a portion of the missing heritability for ADHD. Here we believe we performed the first large-scale next-generation targeted sequencing study of ADHD in 152 child and adolescent cases and 188 controls across an a priori set of 117 genes. A multi-marker gene-level analysis of rare (<1% frequency) single-nucleotide variants (SNVs) revealed that the gene encoding brain-derived neurotrophic factor (BDNF) was associated with ADHD at Bonferroni corrected levels. Sanger sequencing confirmed the existence of all novel rare BDNF variants. Our results implicate BDNF as a genetic risk factor for ADHD, potentially by virtue of its critical role in neurodevelopment and synaptic plasticity.
Subject(s)
Attention Deficit Disorder with Hyperactivity/genetics , Brain-Derived Neurotrophic Factor/genetics , Adolescent , Brain-Derived Neurotrophic Factor/metabolism , Case-Control Studies , Child , DNA , Female , Genetic Predisposition to Disease , Genetic Variation/genetics , Genome-Wide Association Study , Genotype , High-Throughput Nucleotide Sequencing/methods , Humans , Ireland , Male , Polymorphism, Single Nucleotide/genetics , Risk Factors , Sequence Analysis, DNA/methodsABSTRACT
OBJECTIVES: To evaluate endothelial function and vascular stiffness in large, medium, small and microcirculatory blood vessels in very early diffuse systemic sclerosis (SSc). METHODS: We studied consecutive early diffuse SSc patients, defined as <2 years from first SSc symptom who did not have a prior cardiovascular event. Age, gender and race-matched controls were recruited. All underwent assessment of aortic pulse wave velocity (PWV), carotid intima-media thickness (IMT) brachial flow-mediated dilation (FMD), digital peripheral artery tonometer (EndoPAT) assessment and laser speckle contrast imaging (LSCI). RESULTS: Fifteen early diffuse SSc and controls were evaluated. The average age was 49 years, 63% were female and 93% were Caucasian. There were no differences in body mass index, hypertension, diabetes or hyperlipidaemia between controls and SSc patients. Mean SSc disease duration was 1.3 years. In the large central vessels, there was no difference in aortic PWV (p=0.71) or carotid IMT (p=0.92) between SSc patients and controls. Similarly, there was no difference in endothelial dysfunction with brachial artery FMD after ischaemia (p=0.55) and nitroglycerin administration (p=0.74). There were significantly lower values for digital EndoPAT measures (p=0.0001) in SSc patients. LSCI revealed a distinct pattern of microcirculatory abnormalities in response to ischaemia in SSc patients compared to controls. Imaging demonstrated a blunted microcirculatory hyperaemia of the hand with greater subsequent response to nitroglycerin. CONCLUSIONS: These findings suggest that the earliest endothelial changes occur in smaller arterioles and microvascular beds, but not in medium or macrovascular beds, in early diffuse SSc.
Subject(s)
Aorta/physiopathology , Brachial Artery/physiopathology , Endothelium, Vascular/physiopathology , Microvessels/physiopathology , Scleroderma, Diffuse/physiopathology , Vascular Diseases/physiopathology , Vascular Stiffness , Vasodilation/physiology , Adult , Carotid Arteries/diagnostic imaging , Carotid Intima-Media Thickness , Cohort Studies , Female , Fingers/blood supply , Humans , Male , Manometry , Microcirculation/physiology , Middle Aged , Pulse Wave Analysis , Scleroderma, Diffuse/complications , Vascular Diseases/diagnostic imaging , Vascular Diseases/etiologyABSTRACT
Ocular microtremor (OMT) is a small involuntary eye movement present in all subjects. In this paper we present the results of in vivo OMT measurement using a novel non-contact laser speckle technique. OMT signals have not previously been measured from the sclera using this laser speckle correlation technique. To verify the system's ability to record eye movements, it is first tested using a large angle eye rotation. Next, the system is tested with a group of 20 subjects and OMT parameters are extracted. The results of OMT measurements gave a mean frequency of 78 ± 3.86 Hz and peak-to-peak amplitude of 21.42 ± 7.01 µrad, these values are consistent with known values from eye-contacting methods.
Subject(s)
Eye Movement Measurements , Eye Movements , Adult , Blinking , Eye Movement Measurements/instrumentation , Female , Humans , Lasers , Male , Models, Biological , Motion , Saccades , Signal Processing, Computer-Assisted , Time , Young AdultABSTRACT
Schizophrenia (SZ) and autism spectrum disorders (ASDs) are complex neurodevelopmental disorders that may share an underlying pathology suggested by shared genetic risk variants. We sequenced the exonic regions of 215 genes in 147 ASD cases, 273 SZ cases and 287 controls, to identify rare risk mutations. Genes were primarily selected for their function in the synapse and were categorized as: (1) Neurexin and Neuroligin Interacting Proteins, (2) Post-synaptic Glutamate Receptor Complexes, (3) Neural Cell Adhesion Molecules, (4) DISC1 and Interactors and (5) Functional and Positional Candidates. Thirty-one novel loss-of-function (LoF) variants that are predicted to severely disrupt protein-coding sequence were detected among 2 861 rare variants. We found an excess of LoF variants in the combined cases compared with controls (P=0.02). This effect was stronger when analysis was limited to singleton LoF variants (P=0.0007) and the excess was present in both SZ (P=0.002) and ASD (P=0.001). As an individual gene category, Neurexin and Neuroligin Interacting Proteins carried an excess of LoF variants in cases compared with controls (P=0.05). A de novo nonsense variant in GRIN2B was identified in an ASD case adding to the growing evidence that this is an important risk gene for the disorder. These data support synapse formation and maintenance as key molecular mechanisms for SZ and ASD.
Subject(s)
Child Development Disorders, Pervasive/genetics , Genetic Predisposition to Disease/genetics , Mutation/genetics , Nerve Tissue Proteins/genetics , Schizophrenia/genetics , Case-Control Studies , Female , Humans , Male , Middle Aged , White People/geneticsABSTRACT
OBJECTIVE: The purpose of this article is to review new terminology to diagnose, classify, and refer patients with vascular anomalies for additional imaging, intervention, and treatment. CONCLUSION: In recent decades, much has been learned regarding the histopathology, cause, and treatment of vascular anomalies. As information has been gleaned, a new classification system has emerged that divides vascular anomalies into neoplasms and malformations. Its utility is based on accurate initial diagnosis that correlates consistently with clinical presentation, disease course, and treatment.
Subject(s)
Diagnostic Imaging , Neoplasms, Vascular Tissue/classification , Neoplasms, Vascular Tissue/diagnosis , Vascular Malformations/classification , Vascular Malformations/diagnosis , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Referral and Consultation , Terminology as TopicABSTRACT
Recent advances in knowledge regarding histopathology, cause, and treatment of pediatric vascular anomalies have led to substantial changes in classification and terminology. Over the past two decades, various subspecialists have adopted a new classification system proposed by the International Society for the Study of Vascular Anomalies (ISSVA). The ISSVA classification of vascular anomalies divides vascular anomalies into two categories: vascular neoplasms and malformations. It has been widely adopted by various pediatric subspecialists, because it reliably correlates patient presentation and disease progression, with more accurate histology, diagnosis, imaging, and treatment.