Ultra-low-dose cone-beam CT compared to standard dose in the assessment for acute fractures.

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.

Healthy Here: A Promising Referral System Model for Community-Clinical Linkages to Prevent Chronic Disease.

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.

MicroRNA analysis of childhood atopic dermatitis reveals a role for miR-451a.

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.

Tight-Binding Approach to Pyrazine-Mediated Superexchange in Copper-Pyrazine Antiferromagnets.

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.

Securing intraoral skin grafts to the floor of the mouth: case report and technique desription.

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.

Erratum: Dynamical Reduction of the Dimensionality of Exchange Interactions and the "Spin-Liquid" Phase of κ-(BEDT-TTF)_{2}X [Phys. Rev. Lett. 119, 087204 (2017)].

This corrects the article DOI: 10.1103/PhysRevLett.119.087204.

Rare DNA variants in the brain-derived neurotrophic factor gene increase risk for attention-deficit hyperactivity disorder: a next-generation sequencing study.

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.

Dynamical Reduction of the Dimensionality of Exchange Interactions and the "Spin-Liquid" Phase of κ-(BEDT-TTF)_{2}X.

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.

Excess of rare novel loss-of-function variants in synaptic genes in schizophrenia and autism spectrum disorders.

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.

Endothelial dysfunction is present only in the microvasculature and microcirculation of early diffuse systemic sclerosis patients.

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.

Current classification and terminology of pediatric vascular anomalies.

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.

Multifold Fermions and Fermi Arcs Boosted Catalysis in Nanoporous Electride 12CaO·7Al2 O3.

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.

Molecular pathways involved in neuronal cell adhesion and membrane scaffolding contribute to schizophrenia and bipolar disorder susceptibility.

Susceptibility to schizophrenia and bipolar disorder may involve a substantial, shared contribution from thousands of common genetic variants, each of small effect. Identifying whether risk variants map to specific molecular pathways is potentially biologically informative. We report a molecular pathway analysis using the single-nucleotide polymorphism (SNP) ratio test, which compares the ratio of nominally significant (P<0.05) to nonsignificant SNPs in a given pathway to identify the 'enrichment' for association signals. We applied this approach to the discovery (the International Schizophrenia Consortium (n=6909)) and validation (Genetic Association Information Network (n=2729)) of schizophrenia genome-wide association study (GWAS) data sets. We investigated each of the 212 experimentally validated pathways described in the Kyoto Encyclopaedia of Genes and Genomes in the discovery sample. Nominally significant pathways were tested in the validation sample, and five pathways were found to be significant (P=0.03-0.001); only the cell adhesion molecule (CAM) pathway withstood conservative correction for multiple testing. Interestingly, this pathway was also significantly associated with bipolar disorder (Wellcome Trust Case Control Consortium (n=4847)) (P=0.01). At a gene level, CAM genes associated in all three samples (NRXN1 and CNTNAP2), which were previously implicated in specific language disorder, autism and schizophrenia. The CAM pathway functions in neuronal cell adhesion, which is critical for synaptic formation and normal cell signaling. Similar pathways have also emerged from a pathway analysis of autism, suggesting that mechanisms involved in neuronal cell adhesion may contribute broadly to neurodevelopmental psychiatric phenotypes.

IAPP toxicity activates HIF1α/PFKFB3 signaling delaying ß-cell loss at the expense of ß-cell function.

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.

Publisher Correction: IAPP toxicity activates HIF1α/PFKFB3 signaling delaying ß-cell loss at the expense of ß-cell function.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

MDR1/P-glycoprotein and MRP-1 mRNA and protein expression in non-small cell lung cancer.

BACKGROUND: Multiple drug resistance (MDR), both inherent and acquired, is a serious problem in non-small cell lung carcinomas (NSCLC). The purpose of this study was to investigate the prevalence of expression of genes encoding drug efflux pumps, MDR1 and MRP-1, at both the mRNA and protein levels, in this type of cancer. MATERIALS AND METHODS: Tumour specimens (38 cases) were analysed using immunohistochemistry and, where possible (30 cases), also using reverse-transcriptase polymerase chain reaction. RESULTS: The results from this analysis indicated that either, or both, drug efflux pumps were frequently expressed in NSCLC. Expression of mrp1 was found to be predominant over mdr1 at the mRNA level, while MDR1 P-gp was more frequently detected than MRP-1 protein. In some cases, proteins encoding pumps were detected without corresponding mRNAs--possibly due to differing sensitivities of the analysis techniques. CONCLUSION: Future studies of mdr1 and mrp1 using increased-sensitivity qPCR techniques, in parallel with protein analysis, in larger cohorts of cases may help to elucidate the role of drug efflux pumps in NSCLC multiple drug resistance.

Cell cycle-related metabolism and mitochondrial dynamics in a replication-competent pancreatic beta-cell line.

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.

Impacto de la cateterización venosa central percutánea bajo guía ecográfica en una terapia intensiva pediátrica polivalente / Impact of ultrasound-guided percutaneous central venous catheterization at a general pediatric intensive care unit

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)

Nucleotide sequence of the thymidylate synthetase gene (thyP3) from the Bacillus subtilis phage phi 3T.

The thyP3 gene, encoding thymidylate synthetase, from the Bacillus subtilis phage phi 3T has been cloned and the nucleotide sequence determined. The derived amino acid sequence indicates a subunit Mr of 32 748. The primary amino acid sequence is compared with the sequences of the analogous proteins specified by Escherichia coli (thyA), Lactobacillus casei, (thyA) and phage T4 (td). Extensive conservation exists in all four sequences implying a shared tertiary structure.

Mermithid nematode parasites of Coquillettidia perturbans in Massachusetts.

We surveyed 792 larval and 12,400 adult Coquillettidia perturbans for mermithid nematodes in 1990. Collections were made from cattail marshes in the greater Boston area. No mermithids were found in the adult mosquitoes, nor in larvae collected in mid-season, but 3 were found in larvae collected during September and October. This is only the second recorded occurrence of mermithids in Cq. perturbans.