Differentiating neural sensitivity and bias during face-emotion processing in youth: a computational approach.

The ability to interpret face-emotion displays is critical for the development of adaptive social interactions. Using a novel variant of a computational model and fMRI data, we examined behavioral and neural associations between two metrics of face-emotion labeling (sensitivity and bias) and age in youth. Youth and adults (n = 44, M age = 20.02, s.d. = 7.44, range = 8-36) completed an explicit face-emotion labeling fMRI task including happy to angry morphed face emotions. A drift-diffusion model was applied to choice and reaction time distributions to examine sensitivity and bias in interpreting face emotions. Model fit and reliability of parameters were assessed on adult data (n = 42). Linear and quadratic slopes modeled brain activity associated with dimensions of face-emotion valence and ambiguity during interpretation. Behaviorally, age was associated with sensitivity. The bilateral anterior insula exhibited a more pronounced neural response to ambiguity with older age. Associations between sensitivity and bias metrics and activation patterns indicated that systems encoding face-emotion valence and ambiguity both contribute to the ability to discriminate face emotions. The current study provides evidence for age-related improvement in perceptual sensitivity to facial affect across adolescence and young adulthood.

The Developmental Unfolding of ADHD Symptoms from Early Childhood Through Adolescence: Early Effects of Exuberant Temperament, Parenting and Executive Functioning.

Temperament, parenting, and executive functioning (EF) are individual and contextual factors that have been identified to play a role in the development of Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms. Specifically, exuberant temperament in toddlerhood has been associated with both adaptive and maladaptive outcomes, including ADHD symptoms. Therefore, it is important to understand factors that predict which exuberant children experience increased ADHD symptoms and the specific mechanisms through which early exuberant temperament impacts later ADHD symptoms. Using a multi-method, prospective longitudinal design, this study examined a moderated mediation model wherein the interactive effects of observed exuberance and parenting at age 3 predicted the development of parent-reported ADHD symptoms from childhood through adolescence (age 5, 7, 9, 12, and 15) via child EF (i.e., inhibitory control) at age 4. Parent-child dyads (n = 291) from a longitudinal study on child temperament were included. A piecewise model of ADHD symptom growth demonstrated stability in ADHD symptoms from age 5-9 and a decrease from age 9-15. Results support a moderated mediation model wherein an increase in ADHD symptoms throughout childhood was predicted from early childhood exuberant temperament by way of EF, but only for children whose parents displayed less directive parenting. Findings suggest identifiable early markers of risk, including temperament, parenting, and EF- pointing to possible targets for early intervention/prevention.

Effect of a second-generation motion correction algorithm on image quality and measurement reproducibility of coronary CT angiography in patients with a myocardial bridge and mural coronary artery.

AIM: To determine the effect of second-generation motion correction (MC2) on image quality and measurement reproducibility of cardiac CT images in patients with a myocardial bridge and mural coronary artery (MB-MCA) compared to standard (STD) images without motion correction and with first-generation motion correction (MC1). MATERIALS AND METHODS: A total of 66 patients with MB-MCA in the left anterior descending branch who underwent 256-detector CT with single-heartbeat acquisition were included. Images were reconstructed at 45% and 75% R-R intervals using STD, MC1, and MC2 algorithms. Image quality for MB-MCA was assessed by two observers on a four-point scale (1 = poor and 4 = excellent) and compared among STD, MC1, and MC2. Depth and length of MB, lumen area, and minimal diameter of MCA were measured and compared. RESULTS: At 45% R-R interval, image quality scores were 1.59 ± 0.78, 2.21 ± 0.97, and 3.21 ± 0.62 for MCA, and 2.48 ± 0.79, 2.76 ± 0.75, and 3.58 ± 0.58 for MB with STD, MC1 and MC2, respectively. At 75% R-R interval, these values were 2.26 ± 0.60, 3.03 ± 0.89, and 3.59 ± 0.55 for MCA and 3.00 ± 0.93, 3.17 ± 0.83, and 3.80 ± 0.44 for MB. Although MC1 was superior to STD in displaying MCA, there was no statistical difference between the two algorithms for MB (p>0.05). Compared with STD and MC1, MC2 statistically improved image quality and interpretability for both MCA and MB and had narrower limits in interobserver agreement for measurements at both 45% and 75% R-R intervals. CONCLUSION: MC2 improves CT image quality and measurement reproducibility in patients with MB-MCA compared to STD and MC1.

Novel piperazine-1,2,3-triazole leads for the potential treatment of pancreatic cancer.

From lead 1, (N-(4-((4-(3-(4-(3-methoxyphenyl)-1H-1,2,3-triazol-1-yl)propyl)piperazin-1-yl)sulfonyl)-phenyl)acetamide), a S100A2-p53 protein-protein interaction inhibitor based on an in silico modelling driven hypothesis, four focused libraries were designed and synthesised. Growth inhibition screening was performed against 16 human cancer cell lines including the pancreatic cell lines MiaPaCa2, BxPC3, AsPC-1, Capan-2, HPAC, PANC-1 and the drug resistant CFPAC1. Modification of 1's phenylacetamide moiety, gave Library 1 with only modest pancreatic cancer activity. Modification of the 3-OCH3Ph moiety (Library 2) gave 4-CH3 (26), 4-CH2CH3 (27), 4-CF3 (31) and 4-NO2 (32) with sterically bulky groups more active. A 4-CF3 acetamide replacement enhanced cytotoxicity (Library 3). The 4-C(CH3)336 resulted in a predicted steric clash in the S100A2-p53 binding groove, with a potency decrease. Alkyl moieties afforded more potent analogues, 34 (4-CH3) and 35 (CH2CH3), a trend evident against pancreatic cancer: GI50 3.7 (35; BxPC-3) to 18 (40; AsPC-1) µM. Library 4 analogues with a 2-CF3 and 3-CF3 benzenesulfonamide moiety were less active than the corresponding Library 3 analogues. Two additional analogues were designed: 51 (4-CF3; 4-OCH3) and 52 (4-CF3; 2-OCH3) revealed 52 to be 10-20 fold more active than 51, against the pancreatic cancer cell lines examined with sub-micromolar GI50 values 0.43 (HPAC) to 0.61 µM (PANC-1). MOE calculated binding scores for each pose are also consistent with the observed biological activity with 52. The obtained SAR data is consistent with the proposed interaction within the S100A2-p53 bonding groove.

2,3,4',5-Tetrahydroxystilbene-2-O-ß-d-glucoside attenuates atherosclerotic progression by inhibiting inflammation via downregulation of TNF receptor-associated factor 6 expression.

OBJECTIVE: Atherosclerosis (As) is an inflammatory disease, and 2,3,4',5-tetrahydroxystilbene-2-O-ß-d-glucoside (TSG) has been shown to suppress inflammation. However, it is still unclear if TSG alleviates As by inhibiting inflammation. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to assess the mRNA levels of tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), TNF-α and interleukin-6 (IL-6) in lipoprotein E knockout (ApoE -/-) mice with As. Hematoxylin-eosin (H&E) staining was performed to examine the atherosclerotic plaques in the aortic sinus. QRT-PCR and western blotting were used to measure the expression levels of TRAF6, TNF-α, and IL-6 in human umbilical vein endothelial cells (HUVECs), and enzyme-linked immunosorbent assays (ELISAs) were performed to monitor the levels of TNF-α and IL-6 in serum and cell culture medium. RESULTS: TSG inhibited subendothelial plaques formation in the aortic sinus and inhibited the levels of total cholesterol (TCHO), low-density lipoprotein (LDL), TRAF6, TNF-α and IL-6 in AS mice in a dose-dependent manner. Moreover, TSG attenuated the oxidatively modified LDL (ox-LDL)-induced increases in TRAF6, TNF-α and IL-6 expression, whereas TRAF6 overexpression reversed the TSG-induced decreases in TRAF6, TNF-α, and IL-6 expression in HUVECs. CONCLUSIONS: TSG attenuates atherosclerotic progression by inhibiting inflammation via the downregulation of TRAF6 in ApoE-/- mice and HUVECs.

Examining the Relations Between Children's Vagal Flexibility Across Social Stressor Tasks and Parent- and Clinician-Rated Anxiety Using Baseline Data from an Early Intervention for Inhibited Preschoolers.

Early behavioral inhibition (BI) is a known risk factor for later anxiety disorder. Variability in children's parasympathetic nervous system (PNS) functioning may provide insight into the substantial heterogeneity in anxiety outcomes for children high in BI. However, gaps persist due to an over-reliance on static measures of functioning, which limits our ability to leverage PNS functioning to identify risk for anxiety. We address these gaps using baseline data from an early intervention study of inhibited preschoolers by characterizing vagal flexibility (VF), an index of non-linear change in PNS functioning, across social stressor tasks and by examining the associations between VF and anxiety. One hundred and fifty-one parents and their 3.5- to 5-year-old children were selected on the basis of BI to participate in an early intervention program (ClinicalTrials.gov registration: NCT02308826). A structural equation modeling framework was used to model children's VF across tasks designed to mimic exposure to novel social interactions and to test the predictive links between VF and anxiety. Children who showed less VF, characterized by less suppression and flatter recovery, were rated by both parents and clinicians as more anxious. Moreover, a multiple group model showed that children meeting diagnostic criteria for social anxiety disorder demonstrated significantly less VF across social stressor tasks. Among inhibited youth, reduced VF is a risk factor for anxiety and may reflect an individual's reduced capacity to actively cope with external demands. Study results contribute to our understanding of the regulatory processes underlying risk for anxiety in early childhood.

Hydrogel oxygen reservoirs increase functional integration of neural stem cell grafts by meeting metabolic demands.

Injectable biomimetic hydrogels have great potential for use in regenerative medicine as cellular delivery vectors. However, they can suffer from issues relating to hypoxia, including poor cell survival, differentiation, and functional integration owing to the lack of an established vascular network. Here we engineer a hybrid myoglobin:peptide hydrogel that can concomitantly deliver stem cells and oxygen to the brain to support engraftment until vascularisation can occur naturally. We show that this hybrid hydrogel can modulate cell fate specification within progenitor cell grafts, resulting in a significant increase in neuronal differentiation. We find that the addition of myoglobin to the hydrogel results in more extensive innervation within the host tissue from the grafted cells, which is essential for neuronal replacement strategies to ensure functional synaptic connectivity. This approach could result in greater functional integration of stem cell-derived grafts for the treatment of neural injuries and diseases affecting the central and peripheral nervous systems.

Exploratory use of romosozumab for osteoporosis in a patient with Hajdu-Cheney syndrome: a case report.

Hajdu-Cheney syndrome (HCS) is an inherited skeletal disorder caused by mutations in the Notch homolog protein 2 gene (NOTCH2). Treatment of this rare disease is challenging because there are no established guidelines worldwide. Previous case reports using bisphosphonates, denosumab, or teriparatide suggested that curative treatment for HCS did not exist yet in terms of preventing the disease progression. Therefore, the efficacy of romosozumab for osteoporosis in patients with HCS needs to be evaluated. Herein, we report the case of a 43-year-old woman who had progressive acro-osteolysis and repeated fractures since the age of 29 years. Next-generation sequencing confirmed HCS with a mutation at nucleotide 6758G>A, leading to Trp2253Ter replacement in NOTCH2. Romosozumab treatment was initiated because she had already received bisphosphonate for more than 10 years at other hospitals. After 1 year of romosozumab treatment, the bone mineral density (BMD) increased by 10.2%, 6.3%, and 1.3%, with Z scores of -2.9, -1.6, and -1.2 at the lumbar spine, femoral neck, and total hip, respectively. In addition, C-telopeptide was suppressed by 26.4% (0.121 to 0.089 ng/mL), and procollagen type I N-terminal propeptide increased by 18.7% (25.2 to 29.9 ng/mL). This was the first report of romosozumab treatment in patient with osteoporosis and HCS in Korea. One year of romosozumab treatment provided substantial gains in BMD with maintaining the last acro-osteolytic status without deteriorating, representing a possible treatment option for HCS.

Chloride Channel-3 (ClC-3) Modifies the Trafficking of Leucine-Rich Repeat-Containing 8A (LRRC8A) Anion Channels.

Chloride channel-3 (ClC-3) Cl-/H+ antiporters and leucine-rich repeat-containing 8 (LRRC8) family anion channels have both been associated with volume-regulated anion currents (VRACs). VRACs are often altered in ClC-3 null cells but are absent in LRRC8A null cells. To explore the relationship between ClC-3, LRRC8A, and VRAC we localized tagged proteins in human epithelial kidney (HEK293) cells using multimodal microscopy. Expression of ClC-3-GFP induced large multivesicular bodies (MVBs) with ClC-3 in the delimiting membrane. LRRC8A-RFP localized to the plasma membrane and to small cytoplasmic vesicles. Co-expression demonstrated co-localization in small, highly mobile cytoplasmic vesicles that associated with the early endosomal marker Rab5A. However, most of the small LRRC8A-positive vesicles were constrained within large MVBs with abundant ClC-3 in the delimiting membrane. Dominant negative (S34A) Rab5A prevented ClC-3 overexpression from creating enlarged MVBs, while constitutively active (Q79L) Rab5A enhanced this phenotype. Thus, ClC-3 and LRRC8A are endocytosed together but independently sorted in Rab5A MVBs. Subsequently, LRRC8A-labeled vesicles were sorted to MVBs labeled by Rab27A and B exosomal compartment markers, but not to Rab11 recycling endosomes. VRAC currents were significantly larger in ClC-3 null HEK293 cells. This work demonstrates dependence of LRRC8A trafficking on ClC-3 which may explain the association between ClC-3 and VRACs.

Chronic gut inflammation impairs contextual control of fear.

Chronic inflammatory diseases are highly comorbid with anxiety in humans. The extent to which chronic inflammation is responsible for this relationship remains to be determined. We therefore tested the hypothesis that prolonged, but not brief, gut inflammation is sufficient to evoke anxiety-related behaviours in mice. We used the discriminative fear to context conditioning paradigm to assess fear generalization, which is a prominent feature of anxiety disorders. Gut inflammation was induced by exposure to dextran sodium sulfate (DSS) in the drinking water, a well-established rodent model of ulcerative colitis evoking prolonged inflammation. Neither acute (1 × 5 day cycle) nor chronic (3 × 5 day cycles) exposure to DSS affected fear responses when tested shortly after conditioning. Mice in all groups generated more fear responses (freezing) in a chamber previously paired with mild shock, as compared to a chamber with no pairing. This suggests DSS exposure had no effect on acquisition or expression of conditioned fear. Acute and control animals showed this same contextual control of freezing when tested 9 days later. In contrast, at this remote time point, the chronically treated animals exhibited increased freezing in the unpaired chamber such that freezing was equivalent in both contexts. These animals, however, showed intact preference for the unpaired chamber when allowed to freely move between chambers. These data suggest that some mnemonic process engaged after training, such as memory consolidation, is affected by past chronic inflammation so as to generalize negative associations and engage fearful responding in inappropriate contexts, despite intact knowledge that the chambers have different affective associations sufficient for place preference.

Transdiagnostic Implications of Parental Socialization of Child and Adolescent Emotional Development: Commentary and Future Directions.

This special issue consists of 23 articles focusing on parent socialization of emotion in children and adolescents as a transdiagnostic factor for the development of psychopathology. The papers in this special issue span various emotion socialization domains, methodologies, ages, and clinical and non-clinical populations, highlighting the promise, as well as complexities of, such transactional work. Our goals for this commentary include synthesizing the articles, highlighting common themes, and suggesting future research initiatives involving measurement, developmental, and cultural considerations. It is our hope that the research presented in this special issue will inspire future, high-quality research on this topic and ultimately improve outcomes for children and adolescents at risk for poor emotion regulation and psychopathology.

Economic impact of COVID-19 pandemic on healthcare facilities and systems: International perspectives.

International hospitals and healthcare facilities are facing catastrophic financial challenges related to the COVID-19 pandemic. The American Hospital Association estimates a financial impact of $202.6 billion in lost revenue for America's hospitals and healthcare systems, or an average of $50.7 billion per month. Furthermore, it could cost low- and middle-income countries ~ US$52 billion (equivalent to US$8.60 per person) each four weeks to provide an effective healthcare response to COVID-19. In the setting of the largest daily COVID-19 new cases in the US, this burden will influence patient care, surgeries, and surgical outcomes. From a global economic standpoint, The World Bank projects that global growth is projected to shrink by almost 8% with poorer countries feeling most of the impact, and the United Nations projects that it will cost the global economy around 2 trillion dollars this year. Overall, a lack of preparedness was a major contributor to the struggles experienced by healthcare facilities around the world. Items such as personal protective equipment (PPE) for healthcare workers, hospital equipment, sanitizing supplies, toilet paper, and water were in short supply. These deficiencies were exposed by COVID-19 and have prompted healthcare organizations around the world to invent new essential plans for pandemic preparedness. In this paper, we will discuss the economic impact of COVID-19 on US and international hospitals, healthcare facilities, surgery, and surgical outcomes. In the future, the US and countries around the world will benefit from preparing a plan of action to use as a guide in the event of a disaster or pandemic.

Recurrence of carcinoma showing thymus-like differentiation (CASTLE) involving the thyroid gland.

BACKGROUND: Carcinoma showing thymus-like differentiation (CASTLE) in the thyroid gland is a rare disease with generally a favorable prognosis. Treatment with surgery and adjuvant radiotherapy has been shown to improve local control and long-term survival rates. In this report, we present a case of a recurrent thyroid gland CASTLE and review the literature on the diagnosis and treatment of this disease. CASE PRESENTATION: A 60-year-old woman, who was diagnosed with a CASTLE thyroid tumor in 2015, had a total thyroidectomy and was maintained on thyroid hormone replacement (levothyroxine). After 5 years, the patient had a recurrence, in an advanced stage unsuitable for surgery. As the patient declined to undergo radiotherapy, she was followed up without intervention and is currently stable after 15 months. CONCLUSIONS: CASTLE is a rare disease, diagnosed based on postoperative pathology and immunohistochemistry analysis, especially upon CD5 marker. In case of relapse, treatment options include surgery and radiotherapy; however conservative management without intervention is an acceptable alternative in some cases.

Oxidant-resistant LRRC8A/C anion channels support superoxide production by NADPH oxidase 1.

KEY POINTS: LRRC8A-containing anion channels associate with NADPH oxidase 1 (Nox1) and regulate superoxide production and tumour necrosis factor-α (TNFα) signalling. Here we show that LRRC8C and 8D also co-immunoprecipitate with Nox1 in vascular smooth muscle cells. LRRC8C knockdown inhibited TNFα-induced O2•- production, receptor endocytosis, nuclear factor-κB (NF-κB) activation and proliferation while LRRC8D knockdown enhanced NF-κB activation. Significant changes in LRRC8 isoform expression in human atherosclerosis and psoriasis suggest compensation for increased inflammation. The oxidant chloramine-T (ChlorT, 1 mM) weakly (∼25%) inhibited LRRC8C currents but potently (∼80%) inhibited LRRC8D currents. Substitution of the extracellular loop (EL1, EL2) domains of 8D into 8C conferred significantly stronger (69%) ChlorT-dependent inhibition. ChlorT exposure impaired subsequent current block by DCPIB, which occurs through interaction with EL1, further implicating external oxidation sites. LRRC8A/C channels most effectively sustain Nox1 activity at the plasma membrane. This may result from their ability to remain active in an oxidized microenvironment. ABSTRACT: Tumour necrosis factor-α (TNFα) activates NADPH oxidase 1 (Nox1) in vascular smooth muscle cells (VSMCs), producing superoxide (O2•- ) required for subsequent signalling. LRRC8 family proteins A-E comprise volume-regulated anion channels (VRACs). The required subunit LRRC8A physically associates with Nox1, and VRAC activity is required for Nox activity and the inflammatory response to TNFα. VRAC currents are modulated by oxidants, suggesting that channel oxidant sensitivity and proximity to Nox1 may play a physiologically relevant role. In VSMCs, LRRC8C knockdown (siRNA) recapitulated the effects of siLRRC8A, inhibiting TNFα-induced extracellular and endosomal O2•- production, receptor endocytosis, nuclear factor-κB (NF-κB) activation and proliferation. In contrast, siLRRC8D potentiated NF-κB activation. Nox1 co-immunoprecipitated with 8C and 8D, and colocalized with 8D at the plasma membrane and in vesicles. We compared VRAC currents mediated by homomeric and heteromeric LRRC8C and LRRC8D channels expressed in HEK293 cells. The oxidant chloramine T (ChlorT, 1 mM) weakly inhibited 8C, but potently inhibited 8D currents. ChlorT exposure also impaired subsequent current block by the VRAC blocker DCPIB, implicating external sites of oxidation. Substitution of the 8D extracellular loop domains (EL1, EL2) into 8C conferred significantly stronger ChlorT-mediated inhibition of 8C currents. Our results suggest that LRRC8A/C channel activity can be effectively maintained in the oxidized microenvironment expected to result from Nox1 activation at the plasma membrane. Increased ratios of 8D:8C expression may potentially depress inflammatory responses to TNFα. LRRC8A/C channel downregulation represents a novel strategy to reduce TNFα-induced inflammation.

Defining an international cut-off of two-legged countermovement jump power for sarcopenia and dysmobility syndrome.

We aimed to establish jump power cut-offs for the composite outcome of either sarcopenia (EWGSOP2) or dysmobility syndrome using Asian and Caucasian cohorts. Estimated cut-offs were sex specific (women: < 19.0 W/kg; men: < 23.8 W/kg) but not ethnicity specific. Jump power has potential to be used in definitions of poor musculoskeletal health. PURPOSE: Weight-corrected jump power measured during a countermovement jump may be a useful tool to identify individuals with poor musculoskeletal health, but no cut-off values exist. We aimed to establish jump power cut-offs for detecting individuals with either sarcopenia or dysmobility syndrome. METHODS: Age- and sex-matched community-dwelling older adults from two cohorts (University of Wisconsin-Madison [UW], Korean Urban Rural Elderly cohort [KURE], 1:2) were analyzed. Jump power cut-offs for the composite outcome of either sarcopenia defined by EWGSOP2 or dysmobility syndrome were determined. RESULTS: The UW (n = 95) and KURE (n = 190) cohorts were similar in age (mean 75 years) and sex distribution (68% women). Jump power was similar between KURE and UW women (19.7 vs. 18.6 W/kg, p = 0.096) and slightly higher in KURE than UW in men (26.9 vs. 24.8 W/kg, p = 0.050). In UW and KURE, the prevalence of sarcopenia (7.4% in both), dysmobility syndrome (31.6% and 27.9%), or composite of either sarcopenia or dysmobility syndrome (32.6% and 28.4%) were comparable. Low jump power cut-offs for the composite outcome differed by sex but not by ethnicity (< 19.0 W/kg in women; < 23.8 W/kg in men). Low jump power was associated with elevated odds of sarcopenia (adjusted odds ratio [aOR] 4.07), dysmobility syndrome (aOR 4.32), or the composite of sarcopenia or dysmobility syndrome (aOR 4.67, p < 0.01 for all) independent of age, sex, height, and ethnicity. CONCLUSION: Sex-specific jump power cut-offs were found to detect the presence of either sarcopenia or dysmobility syndrome in older adults independent of Asian or Caucasian ethnicity.

The diagnostic value of phase angle, an integrative bioelectrical marker, for identifying individuals with dysmobility syndrome: the Korean Urban-Rural Elderly study.

Low phase angle, a non-invasive bioimpedance marker, is associated with elevated odds of dysmobility syndrome and its components. Phase angle (estimated cutoffs: < 4.8° in men; < 4.5° in women) can be used to detect dysmobility syndrome in community-dwelling older adults as a simple, integrative screening tool. INTRODUCTION: Dysmobility syndrome uses a score-based approach to predict fracture risk that incorporates the concepts of osteoporosis, sarcopenia, and obesity. Low phase angle (PhA), a simple, non-invasive bioelectrical impedance marker, was associated with low lean mass, high fat mass, and poor muscle function. We aimed to investigate the association between PhA and dysmobility syndrome, with the exploration of the diagnostic cutoffs. METHODS: In a community-dwelling Korean older adult cohort, dysmobility syndrome was defined as the presence of ≥ 3 of the following components: osteoporosis, low lean mass, falls in the preceding year, low grip strength, high fat mass, and poor timed up and go performance. RESULTS: Among the 1825 participants (mean age 71.6, women 66.7%), subjects were classified into sex-stratified PhA tertiles. The prevalence of dysmobility syndrome increased from the highest PhA tertile group to the lowest (15.50 to 2.45% in men; 33.41 to 12.25% in women, P for trend < 0.001). The mean PhA values decreased as the dysmobility score increased (5.33° to 4.65° in men; 4.76° to 4.39° in women, P for trend < 0.001). Low PhA (cutoff: < 4.8° in men; < 4.5° in women) was associated with twofold elevated odds of dysmobility syndrome after adjusting for age, sex, and conventional risk factors. Low PhA improved the identification of individuals with dysmobility syndrome when added to the conventional risk model (area under the curve, 0.73 to 0.75, P = 0.002). CONCLUSION: Low PhA was associated with dysmobility syndrome and its components, independent of age, sex, body mass index, nutritional status, and inflammation.

Strong exciton-plasmon coupling in dye-doped film on a planar hyperbolic metamaterial.

We experimentally demonstrate the direct strong coupling between the S0→S1 absorption transition of rhodamine 6G (R6G) dye molecules and the surface plasmon polaritons of a hyperbolic metamaterial (HMM) substrate. The surface plasmon mode was excited by a guided mode of the R6G-doped polymer thin film on the HMM. The coupling strengths of the interactions between the surface plasmon and two molecular exciton modes are greater than the average linewidths of the individual modes indicating a strong coupling regime. This is the first, to the best of our knowledge, experimental demonstration of the direct strong coupling between the resonance mode supported by the HMM and the dye molecules on the HMM surface, not embedded in the HMM structure. The study may provide the foundation for the development of novel planar photonic or electronic devices.

Correlations between exhaled nitric oxide, rs28364072 polymorphism of FCER2 gene, asthma control, and inhaled corticosteroid responsiveness in children with asthma.

In children with asthma, the responsiveness of inhaled corticosteroids (ICS) is depended on asthma endotype and phenotype. This study aimed to describe the clinical and biological characteristics, and its correlation with polymorphism of rs28364072 in FCER2 of asthmatic children. This work aimed to study the correlation between fractional concentration of exhaled nitric oxide (FENO) level and rs28364072 polymorphism of FCER2 gene with ICS responsiveness and disease control in children with asthma. This study was a prospective and descriptive study. All clinical characteristics, FENO, blood eosinophil counts (BEC), skin prick test (SPT), total IgE, asthma control test, and FCER2 gene polymorphism were performed for each patient. One hundred and seven asthmatic children who were over 5 years old (9.2 ± 2.6), were included. Patients with FENO > 20 ppb had higher percentage of positive SPT, total IgE level, and BEC (89.2 vs 80.0%, 851.1 vs 656.9 UI ml-1, and 785 ± 576 G L-1 vs 425 ± 364 G L-1; respectively). Among them, there were 54.2% of homozygous TT, 36.4% of heterozygous TC, and 9.4% of homozygous CC of rs28364072 polymorphism in FCER2. The percentage of patients with controlled asthma was increasing after 1 month and 3 months (47.1% and 58.8%; respectively). During the study, the ICS was decreasing as indicated by asthma control (348 ± 118 mcg at 1st month vs 329 ± 119 mcg at 3rd month; p < 0.05). CC genotype had the lowest level of increasing FEV1 compared to that in genotype TC and TT (8.4% vs 8.7% and 27.1%; p > 0.05 and p < 0.05; respectively). The percentage of polymorphism in rs28364072 of FCER2 was significant higher in patients with controlled asthma compared to uncontrolled asthma. Asthmatic children with high FENO and rs28364072 polymorphism in FCER2 gene are good responders to ICS; however, asthmatic children with homozygous variant CC of rs28364072 are poorly responsive to ICS.

Value of lipocalin 2 as a potential biomarker for bacterial meningitis.

OBJECTIVES: Central nervous system (CNS) infections are common causes of morbidity and mortality worldwide. We aimed to discover protein biomarkers that could rapidly and accurately identify the likely cause of the infections, essential for clinical management and improving outcome. METHODS: We applied liquid chromatography tandem mass spectrometry on 45 cerebrospinal fluid (CSF) samples from a cohort of adults with and without CNS infections to discover potential diagnostic biomarkers. We then validated the diagnostic performance of a selected biomarker candidate in an independent cohort of 364 consecutively treated adults with CNS infections admitted to a referral hospital in Vietnam. RESULTS: In the discovery cohort, we identified lipocalin 2 (LCN2) as a potential biomarker of bacterial meningitis (BM) other than tuberculous meningitis. The analysis of the validation cohort showed that LCN2 could discriminate BM from other CNS infections (including tuberculous meningitis, cryptococcal meningitis and virus/antibody-mediated encephalitis), with sensitivity of 0.88 (95% confident interval (CI), 0.77-0.94), specificity of 0.91 (95% CI, 0.88-0.94) and diagnostic odds ratio of 73.8 (95% CI, 31.8-171.4). LCN2 outperformed other CSF markers (leukocytes, glucose, protein and lactate) commonly used in routine care worldwide. The combination of LCN2, CSF leukocytes, glucose, protein and lactate resulted in the highest diagnostic performance for BM (area under the receiver operating characteristics curve, 0.96; 95% CI, 0.93-0.99). Data are available via ProteomeXchange with identifier PXD020510. CONCLUSIONS: LCN2 is a sensitive and specific biomarker for discriminating BM from a broad spectrum of other CNS infections. A prospective study is needed to assess the diagnostic utility of LCN2 in the diagnosis and management of CNS infections.