TLR2 Derangements Likely Play a Significant Role in the Inflammatory Response and Thrombosis in Patients with Ph(-) Classical Myeloproliferative Neoplasm.

We investigated the role of toll-like receptors (TLRs) in inflammatory pathways in Philadelphia chromosome-negative myeloproliferative neoplasms (Ph(-)MPNs). TLR2 expression was increased in ET, PV, and MPN (grouped as (PV + (ET) + MF)), whereas TLR4 was elevated only in MPN. TLR3, 7, and 9 were not elevated. Cultured monocyte-derived dendritic cells and plasma assays in TLR2-elevated patients were found to secrete more cytokines than those from TLR2-normal patients. These facts suggest that TLR2 is the major inflammatory pathways in MPN. We also measured S100A9 and reactive oxygen species (ROS), revealing increased S100A9 in PV, MF, and MPN, while ROS were only increased in MF. These data suggests that MPNs initially involve TLR2, with minor contributions from TLR4, and with S100A9, leading to ROS formation, JAK2 mutation, and progression to MF or leukemia. Furthermore, patients with JAK2 mutations or leukocytosis exhibited higher TLR2 expression. In leukocyte-platelet interactions, cells from MPN patients displayed a stronger response to a TLR2 agonist than TLR4 agonist. A TLR2 inhibitor (but not a TLR4 inhibitor) attenuated this response. Thrombosis incidence was higher in TLR2-elevated patients (29%) than in TLR2-normal patients (19%). These findings suggest that TLR2 likely contributes to thrombosis in MPN.

Identification and Characterization of Metastasis-Initiating Cells in ESCC in a Multi-Timepoint Pulmonary Metastasis Mouse Model.

Metastasis is the biggest obstacle to esophageal squamous cell carcinoma (ESCC) treatment. Single-cell RNA sequencing analyses are applied to investigate lung metastatic ESCC cells isolated from pulmonary metastasis mouse model at multiple timepoints to characterize early metastatic microenvironment. A small population of parental KYSE30 cell line (Cluster S) resembling metastasis-initiating cells (MICs) is identified because they survive and colonize at lung metastatic sites. Differential expression profile comparisons between Cluster S and other subpopulations identified a panel of 7 metastasis-initiating signature genes (MIS), including CD44 and TACSTD2, to represent MICs in ESCC. Functional studies demonstrated MICs (CD44high) exhibited significantly enhanced cell survival (resistances to oxidative stress and apoptosis), migration, invasion, stemness, and in vivo lung metastasis capabilities, while bioinformatics analyses revealed enhanced organ development, stress responses, and neuron development, potentially remodel early metastasis microenvironment. Meanwhile, early metastasizing cells demonstrate quasi-epithelial-mesenchymal phenotype to support both invasion and anchorage. Multiplex immunohistochemistry (mIHC) staining of 4 MISs (CD44, S100A14, RHOD, and TACSTD2) in ESCC clinical samples demonstrated differential MIS expression scores (dMISs) predict lymph node metastasis, overall survival, and risk of carcinothrombosis.

Simplified Assessment of Radioiodine Biokinetics for Thyroid Cancer Patients: A Practical Approach Using Continuous External Radiation Monitoring.

INTRODUCTION: The biokinetics of radioiodine (RAI) in thyroid cancer patients are complex. This study aims to develop a practical approach for assessing RAI biokinetics to predict patient discharge time and estimate radiation exposure to caregivers. METHODS: We retrospectively reviewed data from patients with differentiated thyroid carcinoma undergoing RAI treatment. Serial radiation dose rates were dynamically collected during hospitalization and fitted to a biexponential model to assess the biokinetic features: RAI uptake fraction of thyroid tissue (Ft) and effective half-life of extra-thyroid tissue (Tet). Correlations with 99mTc thyroid uptake ratio (TcUR), radiation retention ratio (RR), renal function, and body mass index (BMI) were analyzed. RESULTS: Thirty-five patients were enrolled. The derived Ft was 0.08 ± 0.06 and Tet was 7.57 ± 1.45 h. Pearson's correlation analysis revealed a significant association between Ft and both TcUR and RR (p < 0.05), while Tet correlated with renal function and BMI (p < 0.05). CONCLUSION: This novel and practical method assessing RAI biokinetics demonstrates consistency with other parameters and related studies, enhancing the model reliability. It shows promise in predicting an appropriate discharge time and estimating radiation exposure to caregivers, allowing for modifications to radiation protection precautions to follow ALARA principle and minimize the potential risks from radiation exposure.

Lightweight and drift-free magnetically actuated millirobots via asymmetric laser-induced graphene.

Millirobots must have low cost, efficient locomotion, and the ability to track target trajectories precisely if they are to be widely deployed. With current materials and fabrication methods, achieving all of these features in one millirobot remains difficult. We develop a series of graphene-based helical millirobots by introducing asymmetric light pattern distortion to a laser-induced polymer-to-graphene conversion process; this distortion resulted in the spontaneous twisting and peeling off of graphene sheets from the polymer substrate. The lightweight nature of graphene in combine with the laser-induced porous microstructure provides a millirobot scaffold with a low density and high surface hydrophobicity. Magnetically driven nickel-coated graphene-based helical millirobots with rapid locomotion, excellent trajectory tracking, and precise drug delivery ability were fabricated from the scaffold. Importantly, such high-performance millirobots are fabricated at a speed of 77 scaffolds per second, demonstrating their potential in high-throughput and large-scale production. By using drug delivery for gastric cancer treatment as an example, we demonstrate the advantages of the graphene-based helical millirobots in terms of their long-distance locomotion and drug transport in a physiological environment. This study demonstrates the potential of the graphene-based helical millirobots to meet performance, versatility, scalability, and cost-effectiveness requirements simultaneously.

Clinical Evaluation of the BIOFIRE SPOTFIRE Respiratory Panel.

The BIOFIRE SPOTFIRE Respiratory (R) Panel is a novel, in vitro diagnostic PCR assay with 15 pathogen targets. The runtime is about 15 min which is the shortest among similar panels in the market. We evaluated the performance of the SPOTFIRE R Panel with 151 specimens, including 133 collected from the upper respiratory tract (URT), 13 from the lower respiratory tract (LRT) and 5 external quality assessment program (EQAP) samples. The respiratory specimens were enrolled throughout the first two post-COVID-19 influenza seasons in Hong Kong (March to December 2023). For URT specimens, full concordance was observed between the SPOTFIRE R Panel and the standard-of-care FilmArray Respiratory 2.1 plus Panel (RP2.1plus) for 109 specimens (109/133, 81.95%). After discrepant analysis, the SPOTFIRE R Panel identified more pathogens than the RP2.1plus in 15 specimens and vice versa in 3 specimens. The per-target negative and positive percentage agreement (NPA and PPA) were 92.86-100% except the PPA of adenovirus (88.24%). For LRT and EQAP samples, all results were fully concordant. To conclude, the performance of the SPOTFIRE R Panel was comparable to the RP2.1plus.

FASN Inhibition Decreases MHC-I Degradation and Synergizes with PD-L1 Checkpoint Blockade in Hepatocellular Carcinoma.

Immune checkpoint inhibitors (ICI) transformed the treatment landscape of hepatocellular carcinoma (HCC). Unfortunately, patients with attenuated MHC-I expression remain refractory to ICIs, and druggable targets for upregulating MHC-I are limited. Here, we found that genetic or pharmacologic inhibition of fatty acid synthase (FASN) increased MHC-I levels in HCC cells, promoting antigen presentation and stimulating antigen-specific CD8+ T-cell cytotoxicity. Mechanistically, FASN inhibition reduced palmitoylation of MHC-I that led to its lysosomal degradation. The palmitoyltransferase DHHC3 directly bound MHC-I and negatively regulated MHC-I protein levels. In an orthotopic HCC mouse model, Fasn deficiency enhanced MHC-I levels and promoted cancer cell killing by tumor-infiltrating CD8+ T cells. Moreover, the combination of two different FASN inhibitors, orlistat and TVB-2640, with anti-PD-L1 antibody robustly suppressed tumor growth in vivo. Multiplex IHC of human HCC samples and bioinformatic analysis of The Cancer Genome Atlas data further illustrated that lower expression of FASN was correlated with a higher percentage of cytotoxic CD8+ T cells. The identification of FASN as a negative regulator of MHC-I provides the rationale for combining FASN inhibitors and immunotherapy for treating HCC. SIGNIFICANCE: Inhibition of FASN increases MHC-I protein levels by suppressing its palmitoylation and lysosomal degradation, which stimulates immune activity against hepatocellular carcinoma and enhances the efficacy of immune checkpoint inhibition.

Correlates of supportive care needs among Asian Americans with colorectal, liver, or lung cancer from a web-based patient navigation portal intervention: The Patient COUNTS study.

BACKGROUND: Cancer is the leading cause of death among Asian Americans, who often face barriers to cancer care. Cancer supportive care needs among Asian Americans remain understudied. AIMS: We examined cancer supportive care needs and participant factors correlated with these needs, identified profiles of supportive care needs, and examined whether needs profiles are associated with quality of life among Asian American adults. METHODS AND RESULTS: We recruited 47 Asian American adults with colorectal, liver, or lung cancer who spoke Chinese, English, or Vietnamese, and were starting or undergoing cancer treatment. We assessed cancer supportive care needs in four domains: cancer information, daily living, behavioral health, and language assistance. Hierarchical cluster analysis was used to identify clusters of participants based on their supportive need profiles to further examine the association between need profiles and quality of life (QoL) assessed by the Functional Assessment of Cancer Therapy. Participants (mean age = 57.6) included 72% males and 62% spoke English less than very well. Older participants (age ≥ 65) and those with annual income <$50K reported higher daily living needs. Men and younger participants (age < 50) reported higher behavioral health needs. We found three clusters displaying distinct cancer supportive need profiles: Cluster 1 (28% of the sample) displayed high needs across all domains; Cluster 2 (51%) had low needs across all domains; and Cluster 3 (21%) had high needs for cancer information and daily living. Cluster 1 participants reported the lowest QoL. CONCLUSION: Cancer supportive care needs among Asian American patients with colorectal, liver, and lung cancer were associated with patient characteristics and QoL. Understanding cancer supportive care needs will inform future interventions to improve care and QoL for Asian American patients with cancer. CLINICALTRIALS: gov Identifier: NCT03867916.

Enhanced mitophagy driven by ADAR1-GLI1 editing supports the self-renewal of cancer stem cells in HCC.

BACKGROUND AND AIMS: Deregulation of adenosine-to-inosine editing by adenosine deaminase acting on RNA 1 (ADAR1) leads to tumor-specific transcriptome diversity with prognostic values for HCC. However, ADAR1 editase-dependent mechanisms governing liver cancer stem cell (LCSC) generation and maintenance have remained elusive. APPROACH AND RESULTS: RNA-seq profiling identified ADAR1-responsive recoding editing events in HCC and showed editing frequency of GLI1 , rather than transcript abundance was clinically relevant. Functional differences in LCSC self-renewal and tumor aggressiveness between wild-type (GLI1 wt ) and edited GLI1 (GLI1 edit ) were elucidated. We showed that overediting of GLI1 induced an arginine-to-glycine (R701G) substitution, augmenting tumor-initiating potential and exhibiting a more aggressive phenotype. GLI1 R701G harbored weak affinity to SUFU, which in turn, promoted its cytoplasmic-to-nuclear translocation to support LCSC self-renewal by increased pluripotency gene expression. Moreover, editing predisposed to stabilize GLI1 by abrogating ß-TrCP-GLI1 interaction. Integrative analysis of single-cell transcriptome further revealed hyperactivated mitophagy in ADAR1-enriched LCSCs. GLI1 editing promoted a metabolic switch to oxidative phosphorylation to control stress and stem-like state through PINK1-Parkin-mediated mitophagy in HCC, thereby conferring exclusive metastatic and sorafenib-resistant capacities. CONCLUSIONS: Our findings demonstrate a novel role of ADAR1 as an active regulator for LCSCs properties through editing GLI1 in the highly heterogeneous HCC.

Drosophila tweety facilitates autophagy to regulate mitochondrial homeostasis and bioenergetics in Glia.

Mitochondria support the energetic demands of the cells. Autophagic turnover of mitochondria serves as a critical pathway for mitochondrial homeostasis. It is unclear how bioenergetics and autophagy are functionally connected. Here, we identify an endolysosomal membrane protein that facilitates autophagy to regulate ATP production in glia. We determined that Drosophila tweety (tty) is highly expressed in glia and localized to endolysosomes. Diminished fusion between autophagosomes and endolysosomes in tty-deficient glia was rescued by expressing the human Tweety Homolog 1 (TTYH1). Loss of tty in glia attenuated mitochondrial turnover, elevated mitochondrial oxidative stress, and impaired locomotor functions. The cellular and organismal defects were partially reversed by antioxidant treatment. We performed live-cell imaging of genetically encoded metabolite sensors to determine the impact of tty and autophagy deficiencies on glial bioenergetics. We found that tty-deficient glia exhibited reduced mitochondrial pyruvate consumption accompanied by a shift toward glycolysis for ATP production. Likewise, genetic inhibition of autophagy in glia resulted in a similar glycolytic shift in bioenergetics. Furthermore, the survival of mutant flies became more sensitive to starvation, underlining the significance of tty in the crosstalk between autophagy and bioenergetics. Together, our findings uncover the role for tty in mitochondrial homeostasis via facilitating autophagy, which determines bioenergetic balance in glia.

Human Prune Regulates the Metabolism of Mammalian Inorganic Polyphosphate and Bioenergetics.

Inorganic polyphosphate (polyP) is an evolutionarily conserved and ubiquitous polymer that is present in all studied organisms. PolyP consists of orthophosphates (Pi) linked together by phosphoanhydride bonds. The metabolism of polyP still remains poorly understood in higher eukaryotes. Currently, only F0F1-ATP synthase, Nudt3, and Prune have been proposed to be involved in this metabolism, although their exact roles and regulation in the context of polyP biology have not been fully elucidated. In the case of Prune, in vitro studies have shown that it exhibits exopolyphosphatase activity on very short-chain polyP (up to four units of Pi), in addition to its known cAMP phosphodiesterase (PDE) activity. Here, we expand upon studies regarding the effects of human Prune (h-Prune) on polyP metabolism. Our data show that recombinant h-Prune is unable to hydrolyze short (13-33 Pi) and medium (45-160 Pi) chains of polyP, which are the most common chain lengths of the polymer in mammalian cells. Moreover, we found that the knockdown of h-Prune (h-Prune KD) results in significantly decreased levels of polyP in HEK293 cells. Likewise, a reduction in the levels of polyP is also observed in Drosophila melanogaster loss-of-function mutants of the h-Prune ortholog. Furthermore, while the activity of ATP synthase, and the levels of ATP, are decreased in h-Prune KD HEK293 cells, the expression of ATP5A, which is a main component of the catalytic subunit of ATP synthase, is upregulated in the same cells, likely as a compensatory mechanism. Our results also show that the effects of h-Prune on mitochondrial bioenergetics are not a result of a loss of mitochondrial membrane potential or of significant changes in mitochondrial biomass. Overall, our work corroborates the role of polyP in mitochondrial bioenergetics. It also demonstrates a conserved effect of h-Prune on the metabolism of short- and medium-chain polyP (which are the predominant chain lengths found in mammalian cells). The effects of Prune in polyP are most likely exerted via the regulation of the activity of ATP synthase. Our findings pave the way for modifying the levels of polyP in mammalian cells, which could have pharmacological implications in many diseases where dysregulated bioenergetics has been demonstrated.

The Seasonality of Respiratory Viruses in a Hong Kong Hospital, 2014-2023.

We reviewed the multiplex PCR results of 20,127 respiratory specimens tested in a hospital setting from January 2014 to April 2023. The seasonal oscillation patterns of 17 respiratory viruses were studied. Compared with 2014-2019, a prominent drop in PCR positivity (from 64.46-69.21% to 17.29-29.89%, p < 0.001) and virus diversity was observed during the COVID-19 pandemic, with predominance of rhinovirus/enterovirus, sporadic spikes of parainfluenza viruses 3 and 4, respiratory syncytial virus and SARS-CoV-2, and rare detection of influenza viruses, metapneumovirus, adenovirus and coronaviruses. The suppressed viruses appeared to regain activity from the fourth quarter of 2022 when pandemic interventions had been gradually relaxed in Hong Kong. With the co-circulation of SARS-CoV-2 and seasonal respiratory viruses, surveillance of their activity and an in-depth understanding of the clinical outcomes will provide valuable insights for improved public health measures and reducing disease burden.

Loss of Activity-Induced Mitochondrial ATP Production Underlies the Synaptic Defects in a Drosophila Model of ALS.

Mutations in the gene encoding vesicle-associated membrane protein B (VAPB) cause a familial form of amyotrophic lateral sclerosis (ALS). Expression of an ALS-related variant of vapb (vapbP58S ) in Drosophila motor neurons results in morphologic changes at the larval neuromuscular junction (NMJ) characterized by the appearance of fewer, but larger, presynaptic boutons. Although diminished microtubule stability is known to underlie these morphologic changes, a mechanism for the loss of presynaptic microtubules has been lacking. By studying flies of both sexes, we demonstrate the suppression of vapbP58S -induced changes in NMJ morphology by either a loss of endoplasmic reticulum (ER) Ca2+ release channels or the inhibition Ca2+/calmodulin (CaM)-activated kinase II (CaMKII). These data suggest that decreased stability of presynaptic microtubules at vapbP58S NMJs results from hyperactivation of CaMKII because of elevated cytosolic [Ca2+]. We attribute the Ca2+ dyshomeostasis to delayed extrusion of cytosolic Ca2+ Suggesting that this defect in Ca2+ extrusion arose from an insufficient response to the bioenergetic demand of neural activity, depolarization-induced mitochondrial ATP production was diminished in vapbP58S neurons. These findings point to bioenergetic dysfunction as a potential cause for the synaptic defects in vapbP58S -expressing motor neurons.SIGNIFICANCE STATEMENT Whether the synchrony between the rates of ATP production and demand is lost in degenerating neurons remains poorly understood. We report that expression of a gene equivalent to an amyotrophic lateral sclerosis (ALS)-causing variant of vesicle-associated membrane protein B (VAPB) in fly neurons decouples mitochondrial ATP production from neuronal activity. Consequently, levels of ATP in mutant neurons are unable to keep up with the bioenergetic burden of neuronal activity. Reduced rate of Ca2+ extrusion, which could result from insufficient energy to power Ca2+ ATPases, results in the accumulation of residual Ca2+ in mutant neurons and leads to alterations in synaptic vesicle (SV) release and synapse development. These findings suggest that synaptic defects in a model of ALS arise from the loss of activity-induced ATP production.

Multiple growth factors accommodated degradable submicron calcium sulfate hemihydrate/porous hydroxyapatite for dentin-pulp regeneration.

Vital pulp therapy (VPT) has gained significant consideration by utilizing the natural healing capacity of the inflamed pulp in healing process. However, the protective pulp capping materials that facilitate this healing process are still under investigation for the successful promotion of dentin-pulp regeneration. Herein, we developed a bioactive and biodegradable pulp capping material (denoted as sCSHA-GFs) by synthesizing inorganic submicron calcium sulfate hemihydrate (sCS)/porous hydroxyapatite (HA) loaded with growth factors (GFs) such as transforming growth factor-beta 1 (TGF-ß1), fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF). Physiochemical characteristics of submicron CSHA-GFs (sCSHA-GFs) cement were determined. Human dental pulp stem cells (hDPSCs) were used for analyzing their biocompatibility and bioactivity for dentin mineralization. To evaluate the efficacy of sCSHA-GFs, we compared it with a commercial material, mineral trioxide aggregate (MTA), the reference standard used clinically on pulp capping. Our results showed that sCSHA-GFs cement presented good biodegradability with dissolution properties for sustained release of calcium (Ca2+) ions and GFs, and facilitated attachment, proliferation, differentiation and migration of hDPSCs. In addition, sCSHA-GFs cement was found to be more effective than MTA at prolonged incubation time in inducing the mRNA expression levels of odontoblastic differentiation markers, dentin sialophosphoprotein (DSPP) and dentin matrix protein (DMP-1), leading to increased mineralization (with calcium deposits) along with increased alkaline phosphatase (ALP) expressions, evident from Alizarin Red S and ALP staining assays. Our findings suggest that sCSHA-GFs cement may act as a suitable material in VPT for dentin-pulp regeneration.

Patient-reported supportive care needs among Asian American cancer patients.

PURPOSE: Cancer is the leading cause of death for Asian Americans. However, few studies have documented supportive care needs from the perspective of Asian American cancer patients. This study describes the needs reported by Asian American patients with colorectal, liver, or lung cancer over a 6-month period during their treatment. METHODS: Participants were recruited through the Greater Bay Area Cancer Registry and from cancer care providers in San Francisco. Participants self-identified as Asian or Asian American; were age 21 or older; spoke English, Chinese, or Vietnamese; and had stage I-III colon, rectum, liver, or lung cancer. Participants were matched with a language concordant patient navigator who provided support during a 6-month period. Needs were assessed by surveys at baseline, 3, and 6 months. RESULTS: Among 24 participants, 58% were 65 years or older, 42% did not complete high school, and 75% had limited English proficiency (LEP). At baseline, the most prevalent needs were cancer information (79%), nutrition and physical activity (67%), language assistance (54%), and daily living (50%). At the 3- and 6-month follow-up surveys, there was a higher reported need for mental health resources and healthcare access among participants. CONCLUSION: In this pilot study of Asian American cancer patients who predominantly had LEP, participants reported many needs, with cancer information and language assistance as the most prominent. The findings highlight the importance of culturally and linguistically appropriate patient navigators in addressing supportive care needs among cancer patients with LEP. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03867916.

Very-Low-Dose Radiation and Clinical Molecular Nuclear Medicine.

Emerging molecular and precision medicine makes nuclear medicine a de facto choice of imaging, especially in the era of target-oriented medical care. Nuclear medicine is minimally invasive, four-dimensional (space and time or dynamic space), and functional imaging using radioactive biochemical tracers in evaluating human diseases on an anatomically configured image. Many radiopharmaceuticals are also used in therapies. However, there have been concerns over the emission of radiation from the radionuclides, resulting in wrongly neglecting the potential benefits against little or any risks at all of imaging to the patients. The sound concepts of radiation and radiation protection are critical for promoting the optimal use of radiopharmaceuticals to patients, and alleviating concerns from caregivers, nuclear medicine staff, medical colleagues, and the public alike.

Health Within Reach-a Patient-Centered Intervention to Increase Hepatitis B Screening Among Asian Americans: a Randomized Clinical Trial.

BACKGROUND: There are few studies to date of interventions to increase viral hepatitis screening among Asian Americans, who have high rates of chronic hepatitis B (HBV) infection. OBJECTIVE: To develop, implement, and test the efficacy of a mobile application (Hepatitis App) delivered in four languages to increase HBV screening among Asian Americans. DESIGN: Cluster-randomized clinical trial. PARTICIPANTS: Four hundred fifty-two Asian American patients ≥ 18 years of age, who had no prior HBV testing, and received primary care within two healthcare systems in San Francisco, CA. INTERVENTIONS: The intervention group received the Hepatitis App, delivering interactive video education on viral hepatitis in English, Cantonese, Mandarin, or Vietnamese and a provider printout (Provider Alert) and Provider Panel Notification. The comparison group received a mobile application delivering nutrition and physical activity education and Provider Panel Notification. MAIN MEASURES: Primary outcomes were patient-provider discussion about HBV and documentation of a HBV screening test within 3 months post-intervention. Secondary outcome was documentation of an order for a HBV screening test. KEY RESULTS: Participants had a mean age of 57 years and were 64% female, 80% foreign-born, and 44% with limited English fluency. At post-visit, over 80% of intervention participants reported they liked using the Hepatitis App. At 3-month follow-up, the intervention group was more likely than the comparison group (all P < 0.001) to have discussed HBV with their provider (70% vs.16%), have a HBV test ordered (44% vs.10%), and receive a HBV test (38% vs.8%). In multivariable analyses, the intervention odds ratio for HBV test ordering was 7.6 (95% CI: 3.9, 14.8) and test receipt was 7.5 (95% CI: 3.6, 15.5). CONCLUSIONS: A multi-lingual educational intervention using a mobile application in primary care clinics was well received by Asian American patients, enhanced patient-provider communication about HBV, and increased HBV screening. Technology can improve healthcare quality among Asian Americans. TRIAL REGISTRATION: ClinicalTrials.gov NCT02139722 ( https://clinicaltrials.gov/ct2/show/NCT02139722 ).

Effect of a media intervention on hepatitis B screening among Vietnamese Americans.

Objective: There is a lack of controlled studies of community-wide interventions to increase screening for hepatitis B (HBV) among Asian Americans, particularly Vietnamese Americans, who disproportionately suffer from HBV-related illnesses. The objective of our study was to develop, implement, and evaluate the effectiveness of a media campaign to promote HBV screening among Vietnamese Americans.Design: We designed and implemented a three-year media campaign promoting HBV screening among Vietnamese Americans. Evaluation consisted of cross-sectional pre- and post-intervention population-based telephone surveys of Vietnamese Americans adults age 18-64 who spoke English or Vietnamese and lived in the Northern California (intervention) or Greater Washington, D.C. (comparison) communities in 2007 or 2011. Statistical analysis was completed in 2012. The main outcome was self-report of HBV testing, defined as participants answering 'Yes' to the question: 'Have you ever had a blood test to check for hepatitis B?'Results: The sample sizes at pre- and post-intervention were 1,704 and 1,666, respectively. Both communities reported increased exposure to HBV-related booklets, radio and television advertisements, and websites. Only the intervention community reported increased exposure to newspaper elements. HBV screening increased in both communities (intervention: 65.3% to 73.1%, p < 0.01, comparison: 57.7% to 66.0%, p < 0.01). In multivariable analyses, there was no intervention effect. In both communities, exposure to media elements (Odds Ratio 1.26 [95% Confidence Interval: 1.21, 1.31] for each additional element) was significantly associated with screening.Conclusions: Among Vietnamese Americans in 2 large communities, HBV screening rates were sub-optimal. Screening increased in both the intensive media intervention and comparison communities, and exposure to HBV-related media messages was associated with increased screening. Efforts to address HBV screening among Vietnamese Americans should include mass media messaging.

Lycium barbarum extract promotes M2 polarization and reduces oligomeric amyloid-ß-induced inflammatory reactions in microglial cells.

Lycium barbarum (LB) is a traditional Chinese medicine that has been demonstrated to exhibit a wide variety of biological functions, such as antioxidation, neuroprotection, and immune modulation. One of the main mechanisms of Alzheimer's disease is that microglia activated by amyloid beta (Aß) transform from the resting state to an M1 state and release pro-inflammatory cytokines to the surrounding environment. In the present study, immortalized microglial cells were pretreated with L. barbarum extract for 1 hour and then treated with oligomeric Aß for 23 hours. The results showed that LB extract significantly increased the survival of oligomeric Aß-induced microglial cells, downregulated the expression of M1 pro-inflammatory markers (inducible nitric oxide synthase, tumor necrosis factor α, interleukin-6, and interleukin-1ß), and upregulated the expression of M2 anti-inflammatory markers (arginase-1, chitinase-like protein 3, and interleukin-4). LB extract also inhibited the oligomeric Aß-induced secretion of tumor necrosis factor α, interleukin-6, and interleukin-1ß in microglial cells. The results of in vitro cytological experiments suggest that, in microglial cells, LB extract can inhibit oligomeric Aß-induced M1 polarization and concomitant inflammatory reactions, and promote M2 polarization.