Mapping the cellular biogeography of human bone marrow niches using single-cell transcriptomics and proteomic imaging.

Non-hematopoietic cells are essential contributors to hematopoiesis. However, heterogeneity and spatial organization of these cells in human bone marrow remain largely uncharacterized. We used single-cell RNA sequencing (scRNA-seq) to profile 29,325 non-hematopoietic cells and discovered nine transcriptionally distinct subtypes. We simultaneously profiled 53,417 hematopoietic cells and predicted their interactions with non-hematopoietic subsets. We employed co-detection by indexing (CODEX) to spatially profile over 1.2 million cells. We integrated scRNA-seq and CODEX data to link predicted cellular signaling with spatial proximity. Our analysis revealed a hyperoxygenated arterio-endosteal neighborhood for early myelopoiesis, and an adipocytic localization for early hematopoietic stem and progenitor cells (HSPCs). We used our CODEX atlas to annotate new images and uncovered mesenchymal stromal cell (MSC) expansion and spatial neighborhoods co-enriched for leukemic blasts and MSCs in acute myeloid leukemia (AML) patient samples. This spatially resolved, multiomic atlas of human bone marrow provides a reference for investigation of cellular interactions that drive hematopoiesis.

Single-cell multiomics reveals increased plasticity, resistant populations, and stem-cell-like blasts in KMT2A-rearranged leukemia.

KMT2A-rearranged (KMT2A-r) infant acute lymphoblastic leukemia (ALL) is a devastating malignancy with a dismal outcome, and younger age at diagnosis is associated with increased risk of relapse. To discover age-specific differences and critical drivers that mediate poor outcome in KMT2A-r ALL, we subjected KMT2A-r leukemias and normal hematopoietic cells from patients of different ages to single-cell multiomics analyses. We uncovered the following critical new insights: leukemia cells from patients <6 months have significantly increased lineage plasticity. Steroid response pathways are downregulated in the most immature blasts from younger patients. We identify a hematopoietic stem and progenitor-like (HSPC-like) population in the blood of younger patients that contains leukemic blasts and form an immunosuppressive signaling circuit with cytotoxic lymphocytes. These observations offer a compelling explanation for the ability of leukemias in young patients to evade chemotherapy and immune-mediated control. Our analysis also revealed preexisting lymphomyeloid primed progenitors and myeloid blasts at initial diagnosis of B-ALL. Tracking of leukemic clones in 2 patients whose leukemia underwent a lineage switch documented the evolution of such clones into frank acute myeloid leukemia (AML). These findings provide critical insights into KMT2A-r ALL and have clinical implications for molecularly targeted and immunotherapy approaches. Beyond infant ALL, our study demonstrates the power of single-cell multiomics to detect tumor intrinsic and extrinsic factors affecting rare but critical subpopulations within a malignant population that ultimately determines patient outcome.

Attributional styles are associated with care burden in geriatric depression: older adults and their caregivers in Taiwan.

BACKGROUND: Given the rising prevalence of depression among older adults and the associated increase in caregiving responsibilities, understanding factors influencing caregiver burden is crucial. Previous research has not extensively explored the impact of caregivers' attributional styles, that is, how individuals interpret the causes of life events, on their care burden. AIM: This study examined the relationship between caregivers' attributional styles and their care burden for older patients with depression. METHODS: This cross-sectional study enrolled older adults aged ≥ 65 years diagnosed with depression and their caregivers. Depression was diagnosed according to the DSM-V criteria for Major Depressive Disorder or Persistent Depressive Disorder. Caregivers completed the Chinese Depression Caregiver Burden Scale (CDCBS) to assess care burden, the Hamilton Depression Rating Scale (HAM-D) to evaluate patient symptom severity, the Center for Epidemiological Studies Depression Scale (CES-D) for measuring caregivers' depression, and the Chinese Depression Patient Caregiver Attribution Style Scale (CDPCAS) to assess attributional styles. Hierarchical regression analysis was used to identify the factors independently associated with the caregiver's subjectively assessed care burden. RESULTS: The sample included 146 caregivers of geriatric patients with depression. Most depression patients were women (74.7%) with a mean age of 74.3 years, whereas the mean age of caregivers was 57.7 years. Hierarchical regression analysis identified that caregivers' gender (ß = - 0.14, p = .044), educational level (ß = 0.19, p = .008), caregivers' own depression assessed by the Center for Epidemiological Studies Depression Scale (ß = 0.41, p < .001), and attributional styles, particularly manipulation (ß = 0.29, p < .001) and illness/stress attributional style (ß = 0.23, p = .002) as independent factors associated with care burden. Patient symptom severity assessed using the Hamilton Depression Scale was not significantly correlated with care burden after controlling for attributional styles. CONCLUSIONS: Certain attributional styles, particularly the manipulation and illness/stress attributional styles, significantly increased self-reported care burden. These findings highlight the need for educational resources to change the attribution style, along with support systems and accessible mental health services for caregivers to potentially ease the care burden.

Physical and mental health outcomes associated with adolescent E-cigarette use.

INTRODUCTION: Use of electronic cigarettes (e-cigarette) and other electronic nicotine delivery systems (ENDS) among adolescents has increased dramatically, creating a need for research to examine the consequences of e-cigarette use on adolescent health. Given the emergent state of the research literature, this integrative review sought to summarize what is currently known about the physical and mental health outcomes associated with e-cigarette use in an adolescent population, and to identify directions for future research. METHOD: The methodology for this integrative review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A methodical search was conducted in February 2020 in PubMed, CINAHL, and Web of Science databases. To be eligible for inclusion, studies had to address e-cigarette use, have samples that were between 13 and 24 years of age, be published in a peer-reviewed journal, and examine health outcomes associated with e-cigarette use. After the screening process, 18 studies were included. RESULTS: Physical health outcomes associated with e-cigarette use included oral health and respiratory problems as well as nicotine dependence. Mental health outcomes included depression and suicidal ideation. In studies that compared e-cigarette use to conventional cigarette use and non-use, e-cigarettes tended to be associated with more problems than non-use, but fewer problems than conventional cigarette use. Dual use, that is, use of both conventional cigarettes and e-cigarettes, was associated with the greatest harm. CONCLUSION: Although somewhat less harmful than conventional cigarettes, e-cigarette use is related to a variety of negative physical and mental health outcomes among adolescent users.

Genetic Deletion of HLJ1 Does Not Affect Blood Coagulation in Mice.

HLJ1 (also called DNAJB4) is a member of the DNAJ/Hsp40 family and plays an important role in regulating protein folding and activity. However, there is little information about the role of HLJ1 in the regulation of physiological function. In this study, we investigated the role of HLJ1 in blood coagulation using wild-type C57BL/6 mice and HLJ1-null (HLJ1-/-) mice. Western blot analysis and immunohistochemistry were used to assess the expression and distribution of HLJ1 protein, respectively. The tail bleeding assay was applied to assess the bleeding time and blood loss. A coagulation test was used for measuring the activity of extrinsic, intrinsic and common coagulation pathways. Thromboelastography was used to measure the coagulation parameters in the progression of blood clot formation. The results showed that HLJ1 was detectable in plasma and bone marrow. The distribution of HLJ1 was co-localized with CD41, the marker of platelets and megakaryocytes. However, genetic deletion of HLJ1 did not alter blood loss and the activity of extrinsic and intrinsic coagulation pathways, as well as blood clot formation, compared to wild-type mice. Collectively, these findings suggest that, although HLJ1 appears in megakaryocytes and platelets, it may not play a role in the function of blood coagulation under normal physiological conditions.

[Normal and Near Normal Myocardial Perfusion Imaging Data Analysis: Two-Year Major Adverse Cardiac Event].

BACKGROUND: Myocardial perfusion imaging (MPI) is the method most commonly used to assess patients with suspected coronary artery disease for the presence of myocardial ischemia and risk of subsequent adverse cardiac events. Studies are limited on the incidence of major adverse cardiac event (MACE) in patients with normal MPI results. PURPOSE: The aim of this study was to investigate the incidence and risk factors of MACE in patients with normal or near-normal MPI results. METHODS: In this single-center retrospective chart review study, patients who had received MPI tests at a nuclear medicine department of a medical center in 2017 were consecutively enrolled. All of the participants in this study were patients with normal or near-normal MPI results, and were followed for two years to assess the incidence of MACE (death, hospitalized for percutaneous coronary intervention; CABG, heart failure and stroke). Participants with or without MACE were compared to determine whether demographic, comorbidity, and MPI data were significant risk factors. RESULTS: Of the 1,629 participants (age = 70.4 ± 11.3 years, 49.4% male) enrolled, 387 (23.8%) were classified into the normal MPI group and 1,242 (76.2%) were classified into the near-normal MPI group. Notably, 61 participants (15.8%) in the normal MPI group and 206 (16.6%) in the near-normal MPI group experienced MACE events during the two-year follow-up. The risk factors of MACE identified in this study included being older in age, being male, and having poor myocardial perfusion parameters (i.e., ejection fraction) during MPI. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: Over the two-year study period, 15.8% of the participants with normal MPI results and 16.6% of those with near-normal MPI results experienced major adverse cardiac events. Thus, it is critical to inform patients regarding the potential risk of MACE risk and to educate them on how to mitigate this risk by actively managing their hyperlipidemia level and left ventricular ejection fraction.

Cone beam computed tomographic analysis of the spatial limitation during mandibular arch distalization.

BACKGROUND: In the literature, attempts are seldom made to quantify spatial limitation during mandibular arch distalization. This study aimed to investigate the spatial limitations associated with cortical contact with the mandibular second molar during mandibular arch distalization. METHODS: The study population included 67 individuals who had undergone cone beam computed tomography (CBCT) (34 male and 33 female; mean age: 23.9 ± 2.72 years). The total ridge width, alveolar housing width, and root width were measured to evaluate the buccolingual limit. The space distal to the molar root represented the mesiodistal limit. The influence of sex, right versus left side, root-contact condition, malocclusion category, and presence of wisdom teeth were evaluated. RESULTS: The rate of cortical contact was 49.3% before any orthodontic movement. No significant differences were observed in the alveolar width according to sex (male vs female), side assessed (right vs left), wisdom teeth (present vs absent), or malocclusion category. The ridge width and the alveolar width were smaller in the contact group than in the non-contact group (P < 0.01). The group with wisdom teeth showed a larger available distalization distance, but a significant difference was observed only near the alveolar crest. CONCLUSIONS: Both ridge width and available distalization distance were limiting factors for mandibular teeth distalization. For cases in which whole-arch distalization is planned, CBCT is recommended before treatment, especially for non-extraction treatment. This approach ensures safe and predictable tooth movement.

Endothelial Nitric Oxide Mediates the Anti-Atherosclerotic Action of Torenia concolor Lindley var. Formosama Yamazaki.

Torenia concolor Lindley var. formosama Yamazaki ethanolic extract (TCEE) is reported to have anti-inflammatory and anti-obesity properties. However, the effects of TCEE and its underlying mechanisms in the activation of endothelial nitric oxide synthase (eNOS) have not yet been investigated. Increasing the endothelium-derived nitric oxide (NO) production has been known to be beneficial against the development of cardiovascular diseases. In this study, we investigated the effect of TCEE on eNOS activation and NO-related endothelial function and inflammation by using an in vitro system. In endothelial cells (ECs), TCEE increased NO production in a concentration-dependent manner without affecting the expression of eNOS. In addition, TCEE increased the phosphorylation of eNOS at serine 635 residue (Ser635) and Ser1179, Akt at Ser473, calmodulin kinase II (CaMKII) at threonine residue 286 (Thr286), and AMP-activated protein kinase (AMPK) at Thr172. Moreover, TCEE-induced NO production, and EC proliferation, migration, and tube formation were diminished by pretreatment with LY294002 (an Akt inhibitor), KN62 (a CaMKII inhibitor), and compound C (an AMPK inhibitor). Additionally, TCEE attenuated the tumor necrosis factor-α-induced inflammatory response as evidenced by the expression of adhesion molecules in ECs and monocyte adhesion onto ECs. These inflammatory effects of TCEE were abolished by L-NG-nitroarginine methyl ester (an NOS inhibitor). Moreover, chronic treatment with TCEE attenuated hyperlipidemia, systemic and aortic inflammatory response, and the atherosclerotic lesions in apolipoprotein E-deficient mice. Collectively, our findings suggest that TCEE may confer protection from atherosclerosis by preventing endothelial dysfunction.

In vitro evaluation of the hyaluronic acid/alginate composite powder for topical haemostasis and wound healing.

The use of haemostatic agents can provide life-saving treatment for patients who suffer from massive bleeding in both prehospital and intraoperative conditions. However, there are still urgent demands for novel haemostatic materials that exhibit better haemostatic activity, biocompatibility, and biodegradability than existing products. In the present study, we aim to evaluate the feasibility of new wound dressing, RapidClot, for treating uncontrolled haemorrhage through a series of in vitro assessments to determine the swelling ratio, clotting time, enzymatic degradation, haemolytic activity, cytotoxicity, cell proliferation, and migration. The results indicated that the RapidClot revealed better water adsorption capacity and shorter blood clotting time (132.7 seconds) than two commercially available haemostatic agents Celox (378.7 seconds) and WoundSeal (705.3 seconds). Additionally, the RapidClot dressing exhibited a similar level of degradability in the presence of hyaluronidase and lysozyme as that of Celox, whereas negligible degradation of WoundSeal was obtained. Although both Celox and RapidClot revealed a similar level in cell viability (above than 90%) against NIH/3 T3 fibroblasts, improved cell proliferation and migration could be obtained in RapidClot. Taking together, our results demonstrated that RapidClot could possess a great potential for serving as an efficient healing dressing with haemorrhage control ability.

[Intensive Care Unit-Acquired Weakness].

Intensive care unit (ICU)-acquired weakness is a common neuromuscular complication of critical illness that is considered to be associated with prolonged duration on mechanical ventilation and systemic inflammatory response syndrome. In addition, nutrition and metabolic alternations, which are commonly seen in patients in the ICU, may further accelerate muscle wasting and increase the incidence of ICU-acquired weakness. The clinical features of ICU-acquired weakness include acute generalized muscle weakness that develops after the onset of critical illness. Diaphragmatic dysfunction, post-extubation dysphagia, and functional decline also are common in patients with ICU-acquired weakness. As the recovery of these physical functions is lengthy and difficult, a multidisciplinary team management is recommended. This mini-review was conducted to provide a scientific overview for ICU-acquired weakness, including its definition, etiology, diagnosis/screening, impacts, and potential intervention strategies. We hope that increasing the understanding of frontline staff will promote the timely planning and implementation of related screenings and interventions to enhance the functional recovery of patients receiving care in the ICU.

The phosphatase activity of soluble epoxide hydrolase regulates ATP-binding cassette transporter-A1-dependent cholesterol efflux.

The contribution of soluble epoxide hydrolase (sEH) to atherosclerosis has been well defined. However, less is understood about the role of sEH and its underlying mechanism in the cholesterol metabolism of macrophages. The expression of sEH protein was increased in atherosclerotic aortas of apolipoprotein E-deficient mice, primarily in macrophage foam cells. Oxidized low-density lipoprotein (oxLDL) increased sEH expression in macrophages. Genetic deletion of sEH (sEH-/- ) in macrophages markedly exacerbated oxLDL-induced lipid accumulation and decreased the expression of ATP-binding cassette transporters-A1 (ABCA1) and apolipoprotein AI-dependent cholesterol efflux following oxLDL treatment. The down-regulation of ABCA1 in sEH-/- macrophages was due to an increase in the turnover rate of ABCA1 protein but not in mRNA transcription. Inhibition of phosphatase activity, but not hydrolase activity, of sEH decreased ABCA1 expression and cholesterol efflux following oxLDL challenge, which resulted in increased cholesterol accumulation. Additionally, oxLDL increased the phosphatase activity, promoted the sEH-ABCA1 complex formation and decreased the phosphorylated level of ABCA1 at threonine residues. Overexpression of phosphatase domain of sEH abrogated the oxLDL-induced ABCA1 phosphorylation and further increased ABCA1 expression and cholesterol efflux, leading to the attenuation of oxLDL-induced cholesterol accumulation. Our findings suggest that the phosphatase domain of sEH plays a crucial role in the cholesterol metabolism of macrophages.

Genetic deletion of soluble epoxide hydrolase delays the progression of Alzheimer's disease.

BACKGROUND: Soluble epoxide hydrolase (sEH) is a bifunctional enzyme with COOH-terminal hydrolase and NH2-terminal lipid phosphatase activities. It is expressed in various cell types in the brain and is involved in the pathogenesis of inflammatory and neurodegenerative diseases. Alzheimer's disease (AD) is a progressive neuroinflammatory and neurodegenerative disease. However, the pathological significance of sEH and underlying molecular mechanism in AD remain unclear. METHODS: To examine the role of sEH in pathogenesis of AD, we used wild-type (WT) mice, soluble epoxide hydrolase deficient (sEH-/-) and two mouse models of AD, including amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic (APP/PS1 Tg) and APP/PS1 Tg/sEH-/- mice. Western blotting analysis and immunohistochemistry assay were performed to evaluate the protein expression. Locomotion, nesting building ability, Y-maze, and Morris water maze tests were conducted to study mouse behavior. The levels of interleukin (IL)-1ß, IL-4, IL-6, and IL-10 and the activities of NF-κB and nuclear factor of activated T cells (NFAT) were measured by commercial assay kits. The quantitative protein level profiling in the brain lysate was analyzed using LC-MS/MS approaches. RESULTS: We demonstrated that the level of sEH was increased in the brain and predominantly appeared in hippocampal astrocytes of APP/PS1 Tg mice. Genetic ablation of sEH in APP/PS1 Tg mice delayed the progression of AD as evidenced by the alleviation in behavior outcomes and Aß plaque deposition. In addition, loss of the function of sEH in APP/PS1 Tg mice increased astrogliosis and the production of astrocyte-derived anti-inflammatory cytokines including IL-1ß, IL-4, and IL-10, as well as the activity of NF-kB and NFAT. Moreover, analysis of gene ontology in the AD brain revealed that important signaling pathways and processes related to AD pathogenesis such as translational regulation, oxidative stress, cytoskeleton reorganization, and small GTPase signal transduction were altered in APP/PS1 Tg/sEH-/- mice compared with APP/PS1 Tg mice. CONCLUSION: Our results suggest that sEH is a crucial regulator in the progression of AD and might be a potential therapeutic target for the treatment of AD.

Magnetic Resonance Elastography in the Assessment of Acute Effects of Kinesio Taping on Lumbar Paraspinal Muscles.

BACKGROUND: Kinesio tape (KT) is an elastic therapeutic tape used for treating sports-related injuries and a number of other disorders. To date, the objective evidence to link pathophysiological effects and actual reactions triggered by KT is limited. PURPOSE: To explore the effect of KT on the lumbar paraspinal muscles by magnetic resonance (MR) elastography. STUDY TYPE: Prospective observational study. POPULATION: Sixty-six asymptomatic volunteers with 31 women and 35 men. FIELD STRENGTH/SEQUENCE: 3.0T MRI and elastography with vibration frequency of 120 Hz. ASSESSMENT: The 5-cm-width KT with full tension was placed on a single side of the lumbar paraspinal muscle. The taping side and adhering direction were randomly decided. Two rectangular regions of interest (ROIs) of 5- and 2.5-cm-width were positioned at the bilateral paraspinal regions from the L2 to L4 level on the confidence map of MR elastography before and after KT taping. The mean shear stiffness values of the ROIs at the superficial, middle, and deep depths were recorded; then the differences between the taping and reference sides were calculated. STATISTICAL TESTS: Paired t-test and Pearson correlations were used to evaluate the stiffness changes after KT application and intraoperator errors of the stiffness measures on the reference side, respectively. RESULTS: A significant decrease in the muscle stiffness value between taping and reference sides (-0.71 kPa ± 0.60 with KT and -0.25 kPa ± 0.78 without KT, P < 0.0001 for 5-cm ROI; -0.67 kPa ± 1.12 with KT and -0.16 kPa ± 1.17 without KT, P = 0.0004 for 2.5-cm ROI) was found in the superficial depth, but no significant differences in the middle and deep depths (P = 0.25 and P = 0.79 for 5-cm ROI; P = 0.09 and P = 0.67 for 2.5-cm ROI, respectively). There were no significant differences of muscle stiffness differences between gender (P = 0.11 for superficial, P = 0.37 for middle, P = 0.78 for deep) and taping direction (P = 0.18 for superficial, P = 0.13 for middle, P = 0.15 for deep). DATA CONCLUSION: Our results demonstrate that KT can reduce the MR elastography-derived shear stiffness in the superficial depth of paraspinal muscles. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1039-1045.

The association of obesity and coronary artery disease genes with response to SSRIs treatment in major depression.

Selective serotonin reuptake inhibitors (SSRIs) are first-line antidepressants for the treatment of major depressive disorder (MDD). However, treatment response during an initial therapeutic trial is often poor and is difficult to predict. Heterogeneity of response to SSRIs in depressed patients is partly driven by co-occurring somatic disorders such as coronary artery disease (CAD) and obesity. CAD and obesity may also be associated with metabolic side effects of SSRIs. In this study, we assessed the association of CAD and obesity with treatment response to SSRIs in patients with MDD using a polygenic score (PGS) approach. Additionally, we performed cross-trait meta-analyses to pinpoint genetic variants underpinnings the relationship of CAD and obesity with SSRIs treatment response. First, PGSs were calculated at different p value thresholds (PT) for obesity and CAD. Next, binary logistic regression was applied to evaluate the association of the PGSs to SSRIs treatment response in a discovery sample (ISPC, N = 865), and in a replication cohort (STAR*D, N = 1,878). Finally, a cross-trait GWAS meta-analysis was performed by combining summary statistics. We show that the PGSs for CAD and obesity were inversely associated with SSRIs treatment response. At the most significant thresholds, the PGS for CAD and body mass index accounted 1.3%, and 0.8% of the observed variability in treatment response to SSRIs, respectively. In the cross-trait meta-analyses, we identified (1) 14 genetic loci (including NEGR1, CADM2, PMAIP1, PARK2) that are associated with both obesity and SSRIs treatment response; (2) five genetic loci (LINC01412, PHACTR1, CDKN2B, ATXN2, KCNE2) with effects on CAD and SSRIs treatment response. Our findings implicate that the genetic variants of CAD and obesity are linked to SSRIs treatment response in MDD. A better SSRIs treatment response might be achieved through a stratified allocation of treatment for MDD patients with a genetic risk for obesity or CAD.

Facile Fabrication of Triphenylamine-Based Redox-Active Nanocomposites by a Sol-Gel Method: Enhanced Electrochromic Response Capability and Stability Performance.

In this research, a new design of organic-inorganic hybrid networks involving covalently bonding, novel, electron-donating triphenylamine (TPA)-containing electroactive molecules to inorganic metal oxides is successfully developed by using a facile sol-gel process. These anodically electrochromic TPA-containing materials exhibit multicolor electrochromic behaviors at various oxidation states. By introducing zirconium oxide into electrochromic materials, not only can an excellent optical transparency in the visible light region at a neutral state be achieved given the nature of the large energy bandgap, but the electrochromic switching can also be driven by a lower oxidation potential with an enhanced response capability (shorter coloring times and bleaching times). Moreover, the hybrid films show outstanding electrochemical stability and high reversibility under long-term operations owing to their good adhesion to the electrode. Consequently, the electrochromic devices derived from these novel hybrid electroactive materials reveal a huge potential for electrochromic applications.

Unenhanced multidetector computed tomography findings in acute central pulmonary embolism.

BACKGROUND: Computed tomography pulmonary angiography (CTPA) is the gold standard for the diagnosis of pulmonary embolism (PE). However, contrast is contraindicated in some patients. The purpose of this study was to determine the diagnostic accuracy of unenhanced multidetector CT (MDCT) for diagnosis of central PE using CTPA as the gold standard. METHODS: The records of patients with suspected PE seen between 2010 and 2013 were retrospectively reviewed. Inclusion criteria were an acute, central PE confirmed by CTPA and non-enhanced MDCT before contrast injection. Patients with a PE ruled out by CTPA served as a control group. MDCT findings studied were high-attenuation emboli in pulmonary artery (PA), main PA dilatation > 33.2 mm, and peripheral wedge-shaped consolidation. Receiver operating characteristic (ROC) analysis was used to determine the sensitivity and specificity of unenhanced MDCT to detect PE. Wells score of all patients were calculated using data extracted from medical records prior to imaging analysis. RESULTS: Thirty-two patients with a PE confirmed by CTPA and 32 with a PE ruled out by CTPA were included. Among the three main MDCT findings, high-attenuation emboli in the PA showed best diagnostic performance (Sensitivity 72.9%; Specificity 100%), followed by main PA dilatation > 33.2 mm (sensitivity 46.9%; specificity 90.6%), and peripheral wedge-shaped consolidation (sensitivity 43.8%; specificity 78.1%). Given any one or more positive findings on unenhanced MDCT, the sensitivity was 96.9% and specificity was 71.9% for a diagnosis of PE in patients. The area under the curve (AUC) of a composite measure of unenhanced MDCT findings (0.909) was significantly higher than that of the Wells score (0.688), indicating unenhanced MDCT was reliable for detecting PE than Wells score. CONCLUSIONS: Unenhanced MDCT is an alternative for the diagnosis of acute central PE when CTPA is not available.

Regulation of Gap Junction Dynamics by UNC-44/ankyrin and UNC-33/CRMP through VAB-8 in C. elegans Neurons.

Gap junctions are present in both vertebrates and invertebrates from nematodes to mammals. Although the importance of gap junctions has been documented in many biological processes, the molecular mechanisms underlying gap junction dynamics remain unclear. Here, using the C. elegans PLM neurons as a model, we show that UNC-44/ankyrin acts upstream of UNC-33/CRMP in regulation of a potential kinesin VAB-8 to control gap junction dynamics, and loss-of-function in the UNC-44/UNC-33/VAB-8 pathway suppresses the turnover of gap junction channels. Therefore, we first show a signal pathway including ankyrin, CRMP, and kinesin in regulating gap junctions.

Atypical Antipsychotic Drug Olanzapine Deregulates Hepatic Lipid Metabolism and Aortic Inflammation and Aggravates Atherosclerosis.

BACKGROUND/AIMS: Olanzapine, an atypical antipsychotic drug, has therapeutic effects for schizophrenia. However, clinical reports indicate that patients taking atypical antipsychotic drugs are at high risk of metabolic syndrome with unclear mechanisms. We investigated the effect of olanzapine on atherosclerosis and the mechanisms in apolipoprotein E-null (apoE-/-) mice. METHODS: ApoE-/- mice were used as in vivo models. Western blot analysis was used to evaluate protein expression. Conventional assay kits were applied to assess the levels of cholesterol, triglycerides, free cholesterol, cholesteryl ester, fatty acids, glycerol, and cytokines. RESULTS: Daily treatment with olanzapine (3 mg/kg body weight) for four weeks increased mean arterial blood pressure and the whitening of brown adipose tissue in mice. In addition, olanzapine impaired aortic cholesterol homeostasis and exacerbated hyperlipidemia and aortic inflammation, which accelerated atherosclerosis in mice. Moreover, lipid accumulation in liver, particularly total cholesterol, free cholesterol, fatty acids, and glycerol, was increased with olanzapine treatment in apoE-/- mice by upregulating the expression of de novo lipid synthesis-related proteins and downregulating that of cholesterol clearance- or very low-density lipoprotein secretion-related proteins. CONCLUSION: Olanzapine may exacerbate atherosclerosis by deregulating hepatic lipid metabolism and worsening hyperlipidemia and aortic inflammation.

An automatic integrated microfluidic system for allergy microarray chips.

Billions of people suffer from allergies, though in many cases, the source allergen is unknown. If one knows which allergens to avoid, this would result in an improved quality of life. Since a rapid, high-throughput, automatic allergen detection method is of great need, an integrated system combining microfluidic techniques and microarray chips has been developed herein to automate the allergen detection process. The developed microfluidic system could automatically carry out the entire procedure such as reagent incubation, hybridization, transport, and washing without any intermediate step. The microarray chip could be easily detached from the microfluidic chip afterwards, enabling it to be read under a fluorescence scanner. The experimental results indicated that the developed microfluidic system can automatically perform all the incubation processes, including hybridization, reagent transportation, and washing. It is worth noting that active mixing has been applied in the present study which is different from our previous study using micro-channels for passive incubation. Comparable results to a conventional benchtop approach were obtained in ∼30% less time with ∼25% less samples/reagents. Similar results were also demonstrated while detecting immunoglobulin E samples. The developed system could therefore provide a rapid, reliable, and automated approach for detecting allergen-specific antibodies in human serum.

Estimated radiation risk of cancer from dental cone-beam computed tomography imaging in orthodontics patients.

BACKGROUND: Radiation dose evaluation is important to cone-beam computed tomography (CBCT) for routine orthodontic treatment planning, especially for a significant proportion of children in orthodontic patients. This study evaluated the patient radiation dose and estimated the radiation cancer risk on dental CBCT according to the calculations by the Monte Carlo simulation method. METHODS: The dental CBCT scanner evaluated in this project was the i- CAT® (Imaging Sciences International Inc., PA, U.S.A.) device. Organ doses and effective doses were calculated by using personal computer-based Monte Carlo simulation (PCXMC 2.0 Rotation) software. The cancer risk resulting from the exposure to ionizing radiation was estimated by using the BEIR VII (Biologic Effects of Ionizing Radiation VII) report model, and the risk of exposure-induced death (REID) was assessed by PCXMC 2.0 Rotation software. RESULTS: The largest contribution to the organ dose and effective dose at Zref 83 cm positioned in the dental CBCT x-ray beam centerline was from the salivary glands (738.29µGy, 7.38 µSv). The different organ doses showed the maximum values at the different Zref locations, and the largest contribution to the organ dose and effective dose of all simulated positions was from the thyroid (928.77µGy, 37.5 µSv). The REID values in the 10-year olds (22.6 × 10- 7, female; 19 × 10- 7, male) were approximately double than those in 30-year olds (10.4 × 10- 7, female; 8.88 × 10- 7, male) for all cancers. The highest change during age range from 10 to 30 was shown in breast cancer of females. CONCLUSIONS: Although individual cancer risk estimates as a function of gender and age are small, the concern about the risks from dental CBCT is related to the rapid increase in its use for orthodontic practice, especially in children patients.