Vaccine Effectiveness Against Severe Disease and Death for Patients With COVID-19 During the Delta-Dominant and Omicron-Emerging Periods: A K-COVE Study.

National cohort data collected during the coronavirus disease 2019 (COVID-19) delta and omicron periods in Korea revealed a lower risk of severe infection in recipients of three doses of the COVID-19 vaccine (adjusted odds ratio [aOR], 0.05-0.08). The risk of death was reduced during the omicron period compared to the delta period (aOR, 0.75; 95% confidence interval, 0.67-0.84).

Importation and Transmission of SARS-CoV-2 B.1.1.529 (Omicron) Variant of Concern in Korea, November 2021.

In November 2021, 14 international travel-related severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (omicron) variant of concern (VOC) patients were detected in South Korea. Epidemiologic investigation revealed community transmission of the omicron VOC. A total of 80 SARS-CoV-2 omicron VOC-positive patients were identified until December 10, 2021 and 66 of them reported no relation to the international travel. There may be more transmissions with this VOC in Korea than reported.

Neur1 and Neur2 are required for hippocampus-dependent spatial memory and synaptic plasticity.

Neur1 and Neur2, mouse homologs of the Drosophila neur gene, consist of two neuralized homology repeat domains and a RING domain. Both Neur1 and Neur2 are expressed in the whole adult brain and encode E3 ubiquitin ligases, which play a crucial role in the Notch signaling pathways. A previous study reported that overexpression of Neur1 enhances hippocampus-dependent memory, whereas the role of Neur2 remains largely unknown. Here, we aimed to elucidate the respective roles of Neur1 and Neur2 in hippocampus-dependent memory using three lines of genetically modified mice: Neur1 knock-out, Neur2 knock-out, and Neur1 and Neur2 double knock-out (D-KO). Our results showed that spatial memory was impaired when both Neur1 and Neur2 were deleted, but not in the individual knock-out of either Neur1 or Neur2. In addition, basal synaptic properties estimated by input-output relationships and paired-pulse facilitation did not change, but a form of long-term potentiation that requires protein synthesis was specifically impaired in the D-KO mice. These results collectively suggest that Neur1 and Neur2 are crucially involved in hippocampus-dependent spatial memory and synaptic plasticity.

Transient cAMP elevation during systems consolidation enhances remote contextual fear memory.

Memory is stored in our brains over a temporally graded transition. With time, recently formed memories are transformed into remote memories for permanent storage; multiple brain regions, such as the hippocampus and neocortex, participate in this process. In this study, we aimed to understand the molecular mechanism of systems consolidation of memory and to investigate the brain regions that contribute to this regulation. We first carried out a contextual fear memory test using a transgenic mouse line, which expressed exogenously-derived Aplysia octopamine receptors in the forebrain region, such that, in response to octopamine treatment, cyclic adenosine monophosphate (cAMP) levels could be transiently elevated. From this experiment, we revealed that transient elevation of cAMP levels in the forebrain during systems consolidation led to an enhancement in remote fear memory and increased miniature excitatory synaptic currents in layer II/III of the anterior cingulate cortex (ACC). Furthermore, using an adeno-associated-virus-driven DREADD system, we investigated the specific regions in the forebrain that contribute to the regulation of memory transfer into long-term associations. Our results implied that transient elevation of cAMP levels was induced chemogenetically in the ACC, but not in the hippocampus, and showed a significant enhancement of remote memory. This finding suggests that neuronal activation during systems consolidation through the elevation of cAMP levels in the ACC contributes to remote memory enhancement.

Characterization of Brain Dysfunction Induced by Bacterial Lipopeptides That Alter Neuronal Activity and Network in Rodent Brains.

The immunopathological states of the brain induced by bacterial lipoproteins have been well characterized by using biochemical and histological assays. However, these studies have limitations in determining functional states of damaged brains involving aberrant synaptic activity and network, which makes it difficult to diagnose brain disorders during bacterial infection. To address this, we investigated the effect of Pam3CSK4 (PAM), a synthetic bacterial lipopeptide, on synaptic dysfunction of female mice brains and cultured neurons in parallel. Our functional brain imaging using PET with [18F]fluorodeoxyglucose and [18F] flumazenil revealed that the brain dysfunction induced by PAM is closely aligned to disruption of neurotransmitter-related neuronal activity and functional correlation in the region of the limbic system rather than to decrease of metabolic activity of neurons in the injection area. This finding was verified by in vivo tissue experiments that analyzed synaptic and dendritic alterations in the regions where PET imaging showed abnormal neuronal activity and network. Recording of synaptic activity also revealed that PAM reorganized synaptic distribution and decreased synaptic plasticity in hippocampus. Further study using in vitro neuron cultures demonstrated that PAM decreased the number of presynapses and the frequency of miniature EPSCs, which suggests PAM disrupts neuronal function by damaging presynapses exclusively. We also showed that PAM caused aggregation of synapses around dendrites, which may have caused no significant change in expression level of synaptic proteins, whereas synaptic number and function were impaired by PAM. Our findings could provide a useful guide for diagnosis and treatment of brain disorders specific to bacterial infection.SIGNIFICANCE STATEMENT It is challenging to diagnose brain disorders caused by bacterial infection because neural damage induced by bacterial products involves nonspecific neurological symptoms, which is rarely detected by laboratory tests with low spatiotemporal resolution. To better understand brain pathology, it is essential to detect functional abnormalities of brain over time. To this end, we investigated characteristic patterns of altered neuronal integrity and functional correlation between various regions in mice brains injected with bacterial lipopeptides using PET with a goal to apply new findings to diagnosis of brain disorder specific to bacterial infection. In addition, we analyzed altered synaptic density and function using both in vivo and in vitro experimental models to understand how bacterial lipopeptides impair brain function and network.

Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function.

Autism spectrum disorder (ASD) is a group of conditions characterized by impaired social interaction and communication, and restricted and repetitive behaviours. ASD is a highly heritable disorder involving various genetic determinants. Shank2 (also known as ProSAP1) is a multi-domain scaffolding protein and signalling adaptor enriched at excitatory neuronal synapses, and mutations in the human SHANK2 gene have recently been associated with ASD and intellectual disability. Although ASD-associated genes are being increasingly identified and studied using various approaches, including mouse genetics, further efforts are required to delineate important causal mechanisms with the potential for therapeutic application. Here we show that Shank2-mutant (Shank2(-/-)) mice carrying a mutation identical to the ASD-associated microdeletion in the human SHANK2 gene exhibit ASD-like behaviours including reduced social interaction, reduced social communication by ultrasonic vocalizations, and repetitive jumping. These mice show a marked decrease in NMDA (N-methyl-D-aspartate) glutamate receptor (NMDAR) function. Direct stimulation of NMDARs with D-cycloserine, a partial agonist of NMDARs, normalizes NMDAR function and improves social interaction in Shank2(-/-) mice. Furthermore, treatment of Shank2(-/-) mice with a positive allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), which enhances NMDAR function via mGluR5 activation, also normalizes NMDAR function and markedly enhances social interaction. These results suggest that reduced NMDAR function may contribute to the development of ASD-like phenotypes in Shank2(-/-) mice, and mGluR modulation of NMDARs offers a potential strategy to treat ASD.

Health Information Seeking, Source Trust, and Culture: A Comparative Analysis of Health Information Trends and Needs Between Guam and the United States.

UNLABELLED: The Guam population offers a unique glimpse into Americans of Pacific Island ancestry and their communication and information-seeking behaviors, experiences, and needs relevant to cancer. National surveys do not typically include the U.S. territories, so there are limited data on the health and cancer information-seeking behaviors of these populations, in which health disparities persist. To fill this information gap, we conducted a survey on health communication in Guam using a modified version of the Health Information National Trends Survey instrument supplemented with items measuring specific cultural factors and communication practices. The results of the survey (N = 511) revealed some differences in health and cancer information-seeking patterns in Guam and the mainland United States. Sociodemographic variables, including sex, age, education, income, and employment, were significantly associated with health and cancer information seeking and Internet use. Levels of trust in various information sources were differentiated in the Guam and mainland U.S. SAMPLES: Logistic regression models revealed differences in factors predicting health and cancer information seeking and Internet use. The results suggest that these health information-seeking patterns and factors should be taken into account when developing communication strategies for more effective prevention and control programs.

A Multistate Asian-Language Tobacco Quitline: Addressing a Disparity in Access to Care.

OBJECTIVES: We conducted a dissemination and implementation study to translate an intervention protocol for Asian-language smokers from an efficacy trial into an effective and sustainable multistate service. METHODS: Three state tobacco programs (in California, Colorado, and Hawaii) promoted a multistate cessation quitline to 3 Asian-language-speaking communities: Chinese, Korean, and Vietnamese. The California quitline provided counseling centrally to facilitate implementation. Three more states joined the program during the study period (January 2010-July 2012). We assessed the provision of counseling, quitting outcomes, and dissemination of the program. RESULTS: A total of 2004 smokers called for the service, with 88.3% opting for counseling. Among those opting for counseling, the 6-month abstinence rate (18.8%) was similar to results of the earlier efficacy trial (16.4%). CONCLUSIONS: The intervention protocol, based on an efficacy trial, was successfully translated into a multistate service and further disseminated. This project paved the way for the establishment of a national quitline for Asian-language speakers, which serves as an important strategy to address disparities in access to care.

Mind Bomb-2 Regulates Hippocampus-dependent Memory Formation and Synaptic Plasticity.

Notch signaling is a key regulator of neuronal fate during embryonic development, but its function in the adult brain is still largely unknown. Mind bomb-2 (Mib2) is an essential positive regulator of the Notch pathway, which acts in the Notch signal-sending cells. Therefore, genetic deletion of Mib2 in the mouse brain might help understand Notch signaling-mediated cell-cell interactions between neurons and their physiological function. Here we show that deletion of Mib2 in the mouse brain results in impaired hippocampal spatial memory and contextual fear memory. Accordingly, we found impaired hippocampal synaptic plasticity in Mib2 knock-out (KO) mice; however, basal synaptic transmission did not change at the Schaffer collateral-CA1 synapses. Using western blot analysis, we found that the level of cleaved Notch1 was lower in Mib2 KO mice than in wild type (WT) littermates after mild foot shock. Taken together, these data suggest that Mib2 plays a critical role in synaptic plasticity and spatial memory through the Notch signaling pathway.

Social media use, body image, and psychological well-being: a cross-cultural comparison of Korea and the United States.

This study examined the relationships among social media use for information, self-status seeking and socializing, body image, self-esteem, and psychological well-being, and some cultural effects moderating these relationships. Americans (n = 502) and Koreans (n = 518) completed an online survey. The main findings showed that (a) social media use for information about body image is negatively related to body satisfaction in the United States and Korea, while social media use for self-status seeking regarding body image is positively related to body satisfaction only in Korea; and (b) body satisfaction has direct and indirect positive effects on psychological well-being manifested in similar ways in the United States and Korea. Implications and future research directions are discussed.

Plasticity of metabotropic glutamate receptor-dependent long-term depression in the anterior cingulate cortex after amputation.

Long-term depression (LTD) is a key form of synaptic plasticity important in learning and information storage in the brain. It has been studied in various cortical regions, including the anterior cingulate cortex (ACC). ACC is a crucial cortical region involved in such emotion-related physiological and pathological conditions as fear memory and chronic pain. In the present study, we used a multielectrode array system to map cingulate LTD in a spatiotemporal manner within the ACC. We found that low-frequency stimulation (1 Hz, 15 min) applied onto deep layer V induced LTD in layers II/III and layers V/VI. Cingulate LTD requires activation of metabotropic glutamate receptors (mGluRs), while L-type voltage-gated calcium channels and NMDA receptors also contribute to its induction. Peripheral amputation of the distal tail impaired ACC LTD, an effect that persisted for at least 2 weeks. The loss of LTD was rescued by priming ACC slices with activation of mGluR1 receptors by coapplying (RS)-3,5-dihydroxyphenylglycine and MPEP, a form of metaplasticity that involved the activation of protein kinase C. Our results provide in vitro evidence of the spatiotemporal properties of ACC LTD in adult mice. We demonstrate that tail amputation causes LTD impairment within the ACC circuit and that this can be rescued by activation of mGluR1.

Perceived barriers to adopting an Asian-language quitline service: a survey of state funding agencies.

This study examined the perceived barriers to adopting an Asian-language quitline service among agencies that fund current state quitline services across the U.S. A self-administered survey on organizational readiness was sent to the funding agencies of 47 states plus Washington D.C. that currently fund state quitlines in English and Spanish, but not in Asian languages (response rate = 58%). The 2010 Census and the 2009 North American Quitline Consortium Survey were used to obtain the proportion of Asians among the state population and state quitline funding level, respectively. The most frequently cited reasons for not adopting an Asian quitline are: the Asian population in the state would be too small (71.4%), costs of service would be too high (57.1%), and the belief that using third-party translation for counseling is sufficient (39.3%). However, neither the actual proportion of Asians among the state population (range = 0.7% to 7.3%), nor the quitline funding level (range = $0.17 to $20.8 per capita) predicts the reported reasons. The results indicate that quitline funding agencies need more education on the necessity and the feasibility of an Asian-language quitline. Three states are currently participating in a multi-state Asian-language quitline in which each state promotes the service to its residents and one state (CA) provides the services for all the states. This centralized multi-state Asian-language quitline operation, which helps reduce practical barriers in adoption and disparity in access to service, could be extended.

Genetic enhancement of behavioral itch responses in mice lacking phosphoinositide 3-kinase-γ (PI3Kγ).

Phosphoinositide 3-kinases (PI3Ks) are important for synaptic plasticity and various brain functions. The only class IB isoform of PI3K, PI3Kγ, has received the most attention due to its unique roles in synaptic plasticity and cognition. However, the potential role of PI3Kγ in sensory transmission, such as pain and itch has not been examined. In this study, we present the evidence for the first time, that genetic deletion of PI3Kγ enhanced scratching behaviours in histamine-dependent and protease-activated receptor 2 (PAR-2)-dependent itch. In contrast, PI3Kγ-deficient mice did not exhibit enhanced scratching in chloroquine-induced itch, suggesting that PI3Kγ selectively contributes to certain types of behavioal itch response. Furthermore, PI3Kγ-deficient mice exhibited normal acute nociceptive responses to thermal and mechanical noxious stimuli. Behavioral licking responses to intraplantar injections of formalin and mechanical allodynia in a chronic inflammatory pain model (CFA) were also not affected by PI3Kγ gene deletion. Our findings indicate that PI3Kγ selectively contributes to behavioral itching induced by histamine and PAR-2 agonist, but not chloroquine agonist.

Health professional's willingness to advocate for strengthening global commitments to the Paris climate agreement: Findings from a multi-nation survey.

Health professionals have the potential to address the health threats posed by climate change in many ways. This study sought to understand the factors that influence health professionals' willingness to engage in climate advocacy. We hypothesized and tested a model with six antecedent factors predicting willingness to engage in advocacy for strengthening global commitments to the Paris Agreement. Using survey data from members of health professional associations in 12 nations (n = 3,977), we tested the hypothesized relationships with structural equation modeling. All of the hypothesized relationships were confirmed. Specifically, higher rates of perceived expert consensus about human-caused climate change predicted greater climate change belief certainty and belief in human causation. In turn, all three of these factors, including higher levels of perceived health harms from climate change, positively predicted affective involvement with the issue. Affective involvement positively predicted the feeling that health professionals have a responsibility to deal with climate change. Lastly, this sense that climate advocacy is a responsibility of health professionals strongly predicted willingness to advocate. As a unique study of predictors of health professionals' willingness to advocate for climate change, our findings provide unique insight into how an influential set of trusted voices might be activated to address what is arguably the world's most pressing public health threat. Limitations of the study and suggestions for future research are presented, and implications for message development are discussed.

Predicting likelihood of in vivo chemotherapy response in canine lymphoma using ex vivo drug sensitivity and immunophenotyping data in a machine learning model.

We report a precision medicine platform that evaluates the probability of chemotherapy drug efficacy for canine lymphoma by combining ex vivo chemosensitivity and immunophenotyping assays with computational modelling. We isolated live cancer cells from fresh fine needle aspirates of affected lymph nodes and collected post-treatment clinical responses in 261 canine lymphoma patients scheduled to receive at least 1 of 5 common chemotherapy agents (doxorubicin, vincristine, cyclophosphamide, lomustine and rabacfosadine). We used flow cytometry analysis for immunophenotyping and ex vivo chemosensitivity testing. For each drug, 70% of treated patients were randomly selected to train a random forest model to predict the probability of positive Veterinary Cooperative Oncology Group (VCOG) clinical response based on input variables including antigen expression profiles and treatment sensitivity readouts for each patient's cancer cells. The remaining 30% of patients were used to test model performance. Most models showed a test set ROC-AUC > 0.65, and all models had overall ROC-AUC > 0.95. Predicted response scores significantly distinguished (P < .001) positive responses from negative responses in B-cell and T-cell disease and newly diagnosed and relapsed patients. Patient groups with predicted response scores >50% showed a statistically significant reduction (log-rank P < .05) in time to complete response when compared to the groups with scores <50%. The computational models developed in this study enabled the conversion of ex vivo cell-based chemosensitivity assay results into a predicted probability of in vivo therapeutic efficacy, which may help improve treatment outcomes of individual canine lymphoma patients by providing predictive estimates of positive treatment response.

Acculturation and Cancer Risk Behaviors among Pacific Islanders in Hawaii.

Background: To communicate research to the public, the National Cancer Institute developed the Health Information National Trends Survey (HINTS). However, as with most national health surveillance, including the Behavioral Risk Factor Surveillance System, HINTS data are not sufficient to address unique demographic subpopulations such as US Pacific Islanders (PIs). National sampling methods do not adequately reach participants from small, medically underserved populations. Aim: This study aims to document the cancer-relevant knowledge, attitudes, behaviors, and information-seeking practices of PIs in Hawaii (HI). Methods: We conducted a cross-sectional survey during 2017-2018 of Native Hawaiians, Chuukese, and Marshallese in HI using Respondent Driven Sampling (RDS) to recruit these geographically diffuse groups. The modified HINTS survey included questions about cancer knowledge, attitudes and behaviors, health communications, and cultural practices. Results: A total of 515 Native Hawaiians, 305 Chuukese, and 180 Marshallese completed the survey. Differences were found across a variety of cancer-related attitudes, knowledge, and behaviors. These groups also differed regarding acculturation, health locus of control, and trust in medical professionals. Native Hawaiians were significantly more acculturated (P=.0001) than Chuukese or Marshallese and more likely to smoke cigarettes (P=.0001). Among participants aged >50 years, we found no significant differences across ethnic groups (P=.30) for those completing a colon cancer screening (37%). However, only 27% were referred to screening by a physician. Conclusions: Cancer prevention programs are greatly needed for PIs in HI. This study provides knowledge concerning the efficiency of RDS to recruit participants, and the role of culture in communications influencing cancer risk behaviors, which may be generalizable to migrant PIs in the United States.

Cultural Considerations for Conducting the Health Information National Trends Survey with Micronesian Communities: Lessons from a Qualitative Study.

A critical barrier to addressing health disparities among minorities is the lack of data, particularly on Pacific Islanders. Typically, national health surveillance systems do not have the resources to ensure proper representation of these small population groups. This study reports factors that guided the cultural adaptation and administration of the National Cancer Institute's Health Information Trends National Survey (HINTS) for a United States-dwelling Pacific Islander population in Hawai'i. To adapt the survey, four focus groups were conducted with 32 purposively-selected Micronesian migrants. Themes on health, healthcare barriers, cancer and methods to implement the survey were extracted from the analyses of the focus group narratives. Key cultural factors were identified that impact health practices, including religious and cancer fatalism, racism, health locus of control and other barriers. Using information from the focus group participants, the HINTS questionnaire was modified and the survey was implemented. The survey data provided will inform the future delivery of health promotion strategies for this unique medically underserved population.

A novel conditional genetic system reveals that increasing neuronal cAMP enhances memory and retrieval.

Consistent evidence from pharmacological and genetic studies shows that cAMP is a critical modulator of synaptic plasticity and memory formation. However, the potential of the cAMP signaling pathway as a target for memory enhancement remains unclear because of contradictory findings from pharmacological and genetic approaches. To address these issues, we have developed a novel conditional genetic system in mice based on the heterologous expression of an Aplysia octopamine receptor, a G-protein-coupled receptor whose activation by its natural ligand octopamine leads to rapid and transient increases in cAMP. We find that activation of this receptor transgenically expressed in mouse forebrain neurons induces a rapid elevation of hippocampal cAMP levels, facilitates hippocampus synaptic plasticity, and enhances the consolidation and retrieval of fear memory. Our findings clearly demonstrate that acute increases in cAMP levels selectively in neurons facilitate synaptic plasticity and memory, and illustrate the potential of this heterologous system to study cAMP-mediated processes in mammalian systems.

Vascular endothelial growth factor (VEGF) signaling regulates hippocampal neurons by elevation of intracellular calcium and activation of calcium/calmodulin protein kinase II and mammalian target of rapamycin.

The present study was undertaken to characterize neuronal activity-dependent expression and release of vascular endothelial growth factor (VEGF) from rat hippocampal neurons and its contribution to neuronal functions. Increased levels of VEGF164 mRNA were evident both in cultured neurons and slices, but not astrocytes, following membrane depolarization with KCl. Activity-dependent expression of VEGF, as well as its release, was dependent on the activation of the N-methyl-d-aspartate receptors or L-type voltage-activated calcium channels. A brief (10 min) application of recombinant VEGF165 to neurons elicited a slow rise in cytosolic Ca2+ in a VEGFR2 dependent manner. The VEGF-induced Ca2+ responses required Ca2+ influx, phospholipase Cgamma and Ca2+ stores. An inhibitor of transient receptor potential canonical channels reduced the VEGF-induced Ca2+ responses by 50%, suggesting the involvement of transient receptor potential canonical channels in the VEGF-mediated responses. The same brief stimulus with VEGF led to long-term synaptic enhancement dependent on protein synthesis. VEGF had prominent effects on the activation calcium/calmodulin protein kinase II and cAMP responsive element binding protein as well as extracellular signal-regulated protein kinase and mammalian target of rapamycin-all in a VEGFR2 dependent manner. Our findings suggest that VEGF released from neuronal cells plays a local role in Ca2+ influx and synaptic transmission that may influence the generation of long-term changes in synaptic efficacy.

Gateway health behaviors in college students: investigating transfer and compensation effects.

OBJECTIVE: There is a dearth of studies on the mechanisms of multiple risk behaviors, even though these behaviors are significant public health issues. The authors investigated whether health behavior interventions have transfer or compensatory effects on other health behaviors. PARTICIPANTS AND METHODS: The authors looked at transfer and compensation effects of 3 health behaviors (smoking, alcohol use, and physical activity) in a sample of college students aged 18 to 25 years (N = 973; 84% born in the United States; 50% female; 25% Japanese, 19% Caucasian, 16% mixed). RESULTS: The study revealed the following evidence for transfer effects: (1) nonsmokers consume less alcohol, (2) regularly active people smoke less, and (3) nondrinkers smoke less. The authors also found the following compensation effects: (1) regularly active people consume alcohol more frequently; and (2) alcohol drinkers are more active. CONCLUSIONS: Interventions involving college students' smoking, alcohol use, and physical activity need to take into account both transfer and compensation considerations to maximize health impacts.