Ganglioside GD3 regulates neural stem cell quiescence and controls postnatal neurogenesis.

The postnatal neural stem cell (NSC) pool hosts quiescent and activated radial glia-like NSCs contributing to neurogenesis throughout adulthood. However, the underlying regulatory mechanism during the transition from quiescent NSCs to activated NSCs in the postnatal NSC niche is not fully understood. Lipid metabolism and lipid composition play important roles in regulating NSC fate determination. Biological lipid membranes define the individual cellular shape and help maintain cellular organization and are highly heterogeneous in structure and there exist diverse microdomains (also known as lipid rafts), which are enriched with sugar molecules, such as glycosphingolipids. An often overlooked but key aspect is that the functional activities of proteins and genes are highly dependent on their molecular environments. We previously reported that ganglioside GD3 is the predominant species in NSCs and that the reduced postnatal NSC pools are observed in global GD3-synthase knockout (GD3S-KO) mouse brains. The specific roles of GD3 in determining the stage and cell-lineage determination of NSCs remain unclear, since global GD3S-KO mice cannot distinguish if GD3 regulates postnatal neurogenesis or developmental impacts. Here, we show that inducible GD3 deletion in postnatal radial glia-like NSCs promotes NSC activation, resulting in the loss of the long-term maintenance of the adult NSC pools. The reduced neurogenesis in the subventricular zone (SVZ) and the dentate gyrus (DG) of GD3S-conditional-knockout mice led to the impaired olfactory and memory functions. Thus, our results provide convincing evidence that postnatal GD3 maintains the quiescent state of radial glia-like NSCs in the adult NSC niche.

Pilot study of a Spanish language measure of financial toxicity in underserved Hispanic cancer patients with low English proficiency.

Background: Financial toxicity (FT) reflects multi-dimensional personal economic hardships borne by cancer patients. It is unknown whether measures of FT-to date derived largely from English-speakers-adequately capture economic experiences and financial hardships of medically underserved low English proficiency US Hispanic cancer patients. We piloted a Spanish language FT instrument in this population. Methods: We piloted a Spanish version of the Economic Strain and Resilience in Cancer (ENRICh) FT measure using qualitative cognitive interviews and surveys in un-/under-insured or medically underserved, low English proficiency, Spanish-speaking Hispanics (UN-Spanish, n = 23) receiving ambulatory oncology care at a public healthcare safety net hospital in the Houston metropolitan area. Exploratory analyses compared ENRICh FT scores amongst the UN-Spanish group to: (1) un-/under-insured English-speaking Hispanics (UN-English, n = 23) from the same public facility and (2) insured English-speaking Hispanics (INS-English, n = 31) from an academic comprehensive cancer center. Multivariable logistic models compared the outcome of severe FT (score > 6). Results: UN-Spanish Hispanic participants reported high acceptability of the instrument (only 0% responded that the instrument was "very difficult to answer" and 4% that it was "very difficult to understand the questions"; 8% responded that it was "very difficult to remember resources used" and 8% that it was "very difficult to remember the burdens experienced"; and 4% responded that it was "very uncomfortable to respond"). Internal consistency of the FT measure was high (Cronbach's α = 0.906). In qualitative responses, UN-Spanish Hispanics frequently identified a total lack of credit, savings, or income and food insecurity as aspects contributing to FT. UN-Spanish and UN-English Hispanic patients were younger, had lower education and income, resided in socioeconomically deprived neighborhoods and had more advanced cancer vs. INS-English Hispanics. There was a higher likelihood of severe FT in UN-Spanish (OR = 2.73, 95% CI 0.77-9.70; p = 0.12) and UN-English (OR = 4.13, 95% CI 1.13-15.12; p = 0.03) vs. INS-English Hispanics. A higher likelihood of severely depleted FT coping resources occurred in UN-Spanish (OR = 4.00, 95% CI 1.07-14.92; p = 0.04) and UN-English (OR = 5.73, 95% CI 1.49-22.1; p = 0.01) vs. INS-English. The likelihood of FT did not differ between UN-Spanish and UN-English in both models (p = 0.59 and p = 0.62 respectively). Conclusion: In medically underserved, uninsured Hispanic patients with cancer, comprehensive Spanish-language FT assessment in low English proficiency participants was feasible, acceptable, and internally consistent. Future studies employing tailored FT assessment and intervention should encompass the key privations and hardships in this population.

Ganglioside GD3 regulates neural stem cell quiescence and controls postnatal neurogenesis.

The postnatal neural stem cell (NSC) pool hosts quiescent and activated radial glia-like NSCs contributing to neurogenesis throughout adulthood. However, the underlying regulatory mechanism during the transition from quiescent NSCs to activated NSCs in the postnatal NSC niche is not fully understood. Lipid metabolism and lipid composition play important roles in regulating NSC fate determination. Biological lipid membranes define the individual cellular shape and help maintain cellular organization and are highly heterogenous in structure and there exist diverse microdomains (also known as lipid rafts), which are enriched with sugar molecules, such as glycosphingolipids. An often overlooked but key aspect is that the functional activities of proteins and genes are highly dependent upon their molecular environments. We previously reported that ganglioside GD3 is the predominant species in NSCs and that the reduced postnatal NSC pools are observed in global GD3-synthase knockout (GD3S-KO) mouse brains. The specific roles of GD3 in determining the stage and cell-lineage determination of NSCs remain unclear, since global GD3S-KO mice cannot distinguish if GD3 regulates postnatal neurogenesis or developmental impacts. Here we show that inducible GD3 deletion in postnatal radial glia-like NSCs promotes the NSC activation, resulting in the loss of the long-term maintenance of the adult NSC pools. The reduced neurogenesis in the subventricular zone (SVZ) and the dentate gyrus (DG) of GD3S-conditional-knockout mice led to impaired olfactory and memory functions. Thus, our results provide convincing evidence that postnatal GD3 maintains the quiescent state of radial glia-like NSCs in the adult NSC niche.

Restoration of Adult Neurogenesis by Intranasal Administration of Gangliosides GD3 and GM1 in The Olfactory Bulb of A53T Alpha-Synuclein-Expressing Parkinson's-Disease Model Mice.

Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting the body and mind of millions of people in the world. As PD progresses, bradykinesia, rigidity, and tremor worsen. These motor symptoms are associated with the neurodegeneration of dopaminergic neurons in the substantia nigra. PD is also associated with non-motor symptoms, including loss of smell (hyposmia), sleep disturbances, depression, anxiety, and cognitive impairment. This broad spectrum of non-motor symptoms is in part due to olfactory and hippocampal dysfunctions. These non-motor functions are suggested to be linked with adult neurogenesis. We have reported that ganglioside GD3 is required to maintain the neural stem cell (NSC) pool in the subventricular zone (SVZ) of the lateral ventricles and the subgranular layer of the dentate gyrus (DG) in the hippocampus. In this study, we used nasal infusion of GD3 to restore impaired neurogenesis in A53T alpha-synuclein-expressing mice (A53T mice). Intriguingly, intranasal GD3 administration rescued the number of bromodeoxyuridine + (BrdU +)/Sox2 + NSCs in the SVZ. Furthermore, the administration of gangliosides GD3 and GM1 increases doublecortin (DCX)-expressing immature neurons in the olfactory bulb, and nasal ganglioside administration recovered the neuronal populations in the periglomerular layer of A53T mice. Given the relevance of decreased ganglioside on olfactory impairment, we discovered that GD3 has an essential role in olfactory functions. Our results demonstrated that intranasal GD3 infusion restored the self-renewal ability of the NSCs, and intranasal GM1 infusion promoted neurogenesis in the adult brain. Using a combination of GD3 and GM1 has the potential to slow down disease progression and rescue dysfunctional neurons in neurodegenerative brains.

Ganglioside Microdomains on Cellular and Intracellular Membranes Regulate Neuronal Cell Fate Determination.

Gangliosides are sialylated glycosphingolipids (GSLs) with essential but enigmatic functions in brain activities and neural stem cell (NSC) maintenance. Our group has pioneered research on the importance of gangliosides for growth factor receptor signaling and epigenetic regulation of NSC activity and differentiation. The primary localization of gangliosides is on cell-surface microdomains and the drastic dose and composition changes during neural differentiation strongly suggest that they are not only important as biomarkers, but also are involved in modulating NSC fate determination. Ganglioside GD3 is the predominant species in NSCs and GD3-synthase knockout (GD3S-KO) revealed reduction of postnatal NSC pools with severe behavioral deficits. Exogenous administration of GD3 significantly restored the NSC pools and enhanced the stemness of NSCs with multipotency and self-renewal. Since morphological changes during neurogenesis require a huge amount of energy, mitochondrial functions are vital for neurogenesis. We discovered that a mitochondrial fission protein, the dynamin-related protein-1 (Drp1), as a novel GD3-binding protein, and GD3 regulates mitochondrial dynamics. Furthermore, we discovered that GM1 ganglioside promotes neuronal differentiation by an epigenetic regulatory mechanism. Nuclear GM1 binds with acetylated histones on the promoters of N-acetylgalactosaminyltransferase (GalNAcT; GM2 synthase) as well as on the NeuroD1 genes in differentiated neurons. In addition, epigenetic activation of the GalNAcT gene was detected as accompanied by an apparent induction of neuronal differentiation in NSCs responding to an exogenous supplement of GM1. GM1 is indeed localized in the nucleus where it can interact with transcriptionally active histones. Interestingly, GM1 could induce epigenetic activation of the tyrosine hydroxylase (TH) gene, with recruitment of nuclear receptor related 1 (Nurr1, also known as NR4A2), a dopaminergic neuron-associated transcription factor, to the TH promoter region. In this way, GM1 epigenetically regulates dopaminergic neuron specific gene expression. GM1 interacts with active chromatin via acetylated histones to recruit transcription factors at the nuclear periphery, resulting in changes in gene expression for neuronal differentiation. The significance is that multifunctional gangliosides modulate lipid microdomains to regulate functions of important molecules on multiple sites: the plasma membrane, mitochondrial membrane, and nuclear membrane. Versatile gangliosides could regulate functional neurons as well as sustain NSC functions via modulating protein and gene activities on ganglioside microdomains.

Functional Impairment of the Nervous System with Glycolipid Deficiencies.

Patients with nervous system disorders suffer from impaired cognitive, sensory and motor functions that greatly inconvenience their daily life and usually burdens their family and society. It is difficult to achieve functional recovery for the damaged central nervous system (CNS) because of its limited ability to regenerate. Glycosphingolipids (GSLs) are abundant in the CNS and are known to play essential roles in cell-cell recognition, adhesion, signal transduction, and cellular migration, that are crucial in all phases of neurogenesis. Despite intense investigation of CNS regeneration, the roles of GSLs in neural regeneration remain unclear. Here we focus on the respective potentials of glycolipids to promote regeneration and repair of the CNS. Mice lacking glucosylceramide, lactosylceramide or gangliosides show lethal phenotypes. More importantly, patients with ganglioside deficiencies exhibit severe clinical phenotypes. Further, neurodegenerative diseases and mental health disorders are associated with altered GSL expression. Accumulating studies demonstrate that GSLs not only delimit physical regions but also play central roles in the maintenance of the biological functions of neurons and glia. We anticipate that the ability of GSLs to modulate behavior of a variety of molecules will enable them to ameliorate biochemical and neurobiological defects in patients. The use of GSLs to treat such defects in the human CNS will be a paradigm-shift in approach since GSL-replacement therapy has not yet been achieved in this manner clinically.

HPV Vaccination Uptake, Hesitancy, and Refusal: Observations of Health-Care Professionals During the COVID-19 Pandemic.

HPV vaccination is highly effective at preventing several types of cancer; however, vaccine uptake is suboptimal. The COVID-19 pandemic has affected participation in cancer prevention measures such as HPV vaccination. To assess changes and barriers to HPV vaccination during the COVID-19 pandemic, we conducted a statewide cross-sectional survey of health-care professionals (HCPs) in Texas. Specifically, we evaluated changes observed by HCPs regarding HPV vaccination during the COVID-19 pandemic: 1) hesitancy, 2) refusal, and 3) uptake. Decreased HPV vaccination uptake were reported by 19.3% of HCPs, whereas increased HPV vaccination hesitancy and refusal were reported by 17.1% and 14.8% of HCPs in Texas, respectively. The COVID-19 pandemic had a negative impact on HPV vaccination. Our study identified barriers to HPV vaccination that are unique to the COVID-19 pandemic.

Ganglioside GD3 is up-regulated in microglia and regulates phagocytosis following global cerebral ischemia.

Gangliosides, the major sialic-acid containing glycosphingolipids in the mammalian brain, play important roles in brain development and neural functions. Here, we show that the b-series ganglioside GD3 and its biosynthetic enzyme, GD3-synthase (GD3S), were up-regulated predominantly in the microglia of mouse hippocampus from 2 to 7 days following global cerebral ischemia (GCI). Interestingly, GD3S knockout (GD3S-KO) mice exhibited decreased hippocampal neuronal loss following GCI, as compared to wild-type (WT) mice. While comparable levels of astrogliosis and microglial proliferation were observed between WT and GD3S-KO mice, the phagocytic capacity of the GD3S-KO microglia was significantly compromised after GCI. At 2 and 4 days following GCI, the GD3S-KO microglia demonstrated decreased amoebic morphology, reduced neuronal material engulfment, and lower expression of the phagolysosome marker CD68, as compared to the WT microglia. Finally, by using a microglia-primary neuron co-culture model, we demonstrated that the GD3S-KO microglia isolated from mouse brains at 2 days after GCI are less neurotoxic to co-cultured hippocampal neurons than the WT-GCI microglia. Moreover, the percentage of microglia with engulfed neuronal elements in the co-cultured wells was also significantly decreased in the GD3S-KO mice after GCI. Interestingly, the impaired phagocytic capacity of GD3S-KO microglia could be partially restored by pre-treatment with exogenous ganglioside GD3. Altogether, this study provides functional evidence that ganglioside GD3 regulates phagocytosis by microglia in an ischemic stroke model. Our data also suggest that the GD3-linked microglial phagocytosis may contribute to the mechanism of delayed neuronal death following ischemic brain injury.

Trends in the rates of health-care providers' recommendation for HPV vaccine from 2012 to 2018: a multi-round cross-sectional analysis of the health information national trends survey.

The 2012 report of the President's Cancer Panel highlighted the overriding contribution of missed clinical opportunities to suboptimal HPV vaccination coverage. Since then, it remains unknown whether the rates of provider recommendations for the HPV vaccine in the US population have increased. We conducted an analysis of four rounds of the Health Information National Trends Survey (HINTS), a household survey of civilian US residents aged 18 y or older. A total of 1,415 (2012), 1,476 (2014), 1,208 (2017), and 1,344 (2018) respondents to the HINTS survey who were either HPV vaccine-eligible or living with HPV vaccine-eligible individuals were included. Overall, the rates of providers' recommendations remained stagnated from 2012 to 2018 in all categories of the study population, except for non-Hispanic Blacks (NHBs), where this prevalence increased during the study period (AAPC = 16.4%, p < .001). In vaccine-eligible individuals (18-27 y), declining trends were noted overall (AAPC = -21.6%, p < .001), among NHWs (AAPC = -30.2%, p < .001) and urban dwellers (AAPC = -21.4%, p < .001). Among vaccine-ineligible respondents (˃27 y) living with vaccine-eligible individuals, trends in the prevalence of provider recommendations for HPV vaccine were stagnating overall (AAPC = 0.5%, p = .90), and increasing only among NHBs (AAPC = 13.9%, p < .001). Despite recent progress, our findings indicate variations of trends in provider recommendations for the HPV vaccine in the US adult population according to age, sex, race/ethnicity, and residence. To accelerate HPV vaccination uptake, immediate actions to enhance provider recommendation for HPV vaccine are needed.

Intranasal infusion of GD3 and GM1 gangliosides downregulates alpha-synuclein and controls tyrosine hydroxylase gene in a PD model mouse.

Parkinson's disease (PD) is characterized by Lewy bodies (composed predominantly of alpha-synuclein [aSyn]) and loss of pigmented midbrain dopaminergic neurons comprising the nigrostriatal pathway. Most PD patients show significant deficiency of gangliosides, including GM1, in the brain, and GM1 ganglioside appears to keep dopaminergic neurons functioning properly. Thus, supplementation of GM1 could potentially provide some rescuing effects. In this study, we demonstrate that intranasal infusion of GD3 and GM1 gangliosides reduces intracellular aSyn levels. GM1 also significantly enhances expression of tyrosine hydroxylase (TH) in the substantia nigra pars compacta of the A53T aSyn overexpressing mouse, following restored nuclear expression of nuclear receptor related 1 (Nurr1, also known as NR4A2), an essential transcription factor for differentiation, maturation, and maintenance of midbrain dopaminergic neurons. GM1 induces epigenetic activation of the TH gene, including augmentation of acetylated histones and recruitment of Nurr1 to the TH promoter region. Our data indicate that intranasal administration of gangliosides could reduce neurotoxic proteins and restore functional neurons via modulating chromatin status by nuclear gangliosides.

Association of dual and poly tobacco use with depressive symptoms and use of antidepressants.

BACKGROUND: There is an established link between depression and tobacco use among adults; however, to date, research has not explored the association of use of dual/poly tobacco products with symptoms and use of medication for depression. METHODS: Data were derived from a 2018 Texas population health assessment survey (n = 2034). Multivariable logistic and multinomial regressions were used to examine for associations between self-reported symptoms of depression and use of prescription medications for depression with use of dual/poly tobacco products. RESULTS: About 20% of adults used one tobacco product, while 9.7% used two or more products. Compared to those without depressive symptoms, those with depressive symptoms had greater odds of single (aOR: 1.66, 95% CI; 1.21 - 2.29) or dual/poly (aOR: 3.09, 95% CI; 1.92 - 4.96) tobacco product use relative to non-users; and relative to single product use, those with depressive symptoms had greater odds of dual/poly tobacco product use (aOR: 2.07; 95% CI, 1.30 - 3.32). Compared to those not using medication for depression, use of medication for depression was associated with a 1.80 (95% CI: 1.15 - 2.84) greater odds of dual/poly tobacco product use relative to non-users; and a 1.91 (95% CI: 1.14 - 3.19) greater odds of dual/poly product use relative to single product users. CONCLUSIONS: Study findings call for primary care providers and psychiatrists to expand screening of individuals experiencing depressive symptoms and using medication for depression, to include assessment for dual/poly tobacco product use.

Genetic determinants of immune-related adverse events in patients with melanoma receiving immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause profound immune-related adverse events (irAEs). The host genetic background is likely to play a role in irAE susceptibility because the presentation of toxicity varies among patients and many do not develop irAEs despite continued ICI use. We sought to identify potential genetic markers conferring risk for irAEs. METHODS: We conducted a pilot exploratory study in 89 melanoma patients who received ICIs (44 with irAEs, and 45 without irAEs after at least 1 year from starting treatment). Genotyping was performed using the Infinium Multi-Ethnic Global-8 v1.0 Bead Chip. The genotype data were extracted using PLINK (v1.90b3.34) and processed for quality control. Population structure-based clustering was carried out using IBS matrix, pairwise population concordance test (p < 1 × 10-3), and phenotype distribution for all study participants, resulting in seven population structure-based clusters. In the analytical stage, 599,931 variants in autosomal chromosomes were included for the association study. The association test was performed using an additive genetic model with exact logistic regression, adjusted for age, sex, and population cluster. RESULTS: A total of 30 variants or single-nucleotide polymorphisms with p < 1 × 10-4 were identified; 12 were associated with an increased risk of irAEs, and the remaining 18 were associated with a decreased risk. Overall, nine of the identified single-nucleotide polymorphisms mapped to eight unique genes that have been associated with autoimmunity or inflammatory diseases. CONCLUSION: Several genetic variants associated with irAEs were identified. Additional larger studies are needed to validate these findings and establish their potential functional relevance.

Ganglioside GD3 regulates dendritic growth in newborn neurons in adult mouse hippocampus via modulation of mitochondrial dynamics.

Ganglioside GD3, a major ganglioside species in neural stem cells, plays a crucial role in maintenance of the self-renewal capacity of these cells. However, its bioactivity in postnatally differentiated neurons in the neurogenic regions of adult brains has not been elucidated. Here, we describe for the first time that deletion of GD3 not only impairs neurotrophin-induced stem cell proliferation, but also alters the dendritic structure as well as the number of synapses of nascent neurons in the dentate gyrus of adult brain. When examining the behavioral phenotypes, GD3 synthase-knockout (GD3S-KO) mice displayed impairment in hippocampus-dependent memory function. To further gain insight into its cellular function, we examined GD3-binding partners from mouse brain extract using a GD3-specific monoclonal antibody, R24, followed by LC-MS/MS analysis and identified a mitochondrial fission protein, the dynamin-related protein-1 (Drp1), as a novel GD3-binding protein. Biochemical and imaging analyses revealed mitochondrial fragmentation in GD3-depleted dentate gyrus neurons, suggesting that GD3 is essential for the mitochondrial Drp1 turnover that is required for efficient mitochondrial fission. These results suggest that GD3 is required for proper dendritic and spine maturation of newborn neurons in adult brain through the regulation of mitochondrial dynamics.

Association of Glycolipids and Growth Factor Receptors in Lipid Rafts.

The traditional methods to study lipid rafts and their association with membrane proteins are based mainly on the isolation of a detergent-resistant membrane by biochemical fractionation. However, the use of detergents may induce lipid segregation and/or redistribution of membrane proteins during the process of sample preparation. Here, we describe a detergent-free method to study the glycolipid and growth factor receptor interaction and their association with lipid rafts. This method combines the biochemical and immunoblotting tools with confocal microscopic imaging, which allows for evaluation and verification of the membrane protein interaction and association with the lipid rafts components in a multifaceted manner.

Distinctive sphingolipid patterns in chronic multiple sclerosis lesions.

Multiple sclerosis (MS) is a CNS disease characterized by immune-mediated demyelination and progressive axonal loss. MS-related CNS damage and its clinical course have two main phases: active and inactive/progressive. Reliable biomarkers are being sought to allow identification of MS pathomechanisms and prediction of its course. The purpose of this study was to identify sphingolipid (SL) species as candidate biomarkers of inflammatory and neurodegenerative processes underlying MS pathology. We performed sphingolipidomic analysis by HPLC-tandem mass spectrometry to determine the lipid profiles in post mortem specimens from the normal-appearing white matter (NAWM) of the normal CNS (nCNS) from subjects with chronic MS (active and inactive lesions) as well as from patients with other neurological diseases. Distinctive SL modification patterns occurred in specimens from MS patients with chronic inactive plaques with respect to NAWM from the nCNS and active MS (Ac-MS) lesions. Chronic inactive MS (In-MS) lesions were characterized by decreased levels of dihydroceramide (dhCer), ceramide (Cer), and SM subspecies, whereas levels of hexosylceramide and Cer 1-phosphate (C1P) subspecies were significantly increased in comparison to NAWM of the nCNS as well as Ac-MS plaques. In contrast, Ac-MS lesions were characterized by a significant increase of major dhCer subspecies in comparison to NAWM of the nCNS. These results suggest the existence of different SL metabolic pathways in the active versus inactive phase within progressive stages of MS. Moreover, they suggest that C1P could be a new biomarker of the In-MS progressive phase, and its detection may help to develop future prognostic and therapeutic strategies for the disease.

Enhanced Susceptibility to Chemoconvulsant-Induced Seizures in Ganglioside GM3 Synthase Knockout Mice.

Ganglioside GM3 synthase (α-2,3-sialyltransferase, ST3GAL5, GM3S) is a key enzyme involved in the biosynthesis of gangliosides. ST3GAL5 deficiency causes an absence of GM3 and all downstream biosynthetic derivatives. The affected individuals manifest deafness, severe irritability, intractable seizures, and profound intellectual disability. To investigate whether deficiency of GM3 is involved in seizure susceptibility, we induced seizures with different chemoconvulsants in ST3GAL5 knockout mice. We report here that ST3GAL5 knockout mice are hyperactive and more susceptible to seizures induced by chemoconvulsants, including kainate and pilocarpine, compared with normal controls. In the hippocampal dentate gyrus, loss of GM3 aggravates seizure-induced aberrant neurogenesis. These data indicate that GM3 and gangliosides derived from GM3 may serve as important regulators of epilepsy and may play an important role in aberrant neurogenesis associated with seizures.

Association of Exposure to Court-Ordered Tobacco Industry Antismoking Advertisements With Intentions and Attempts to Quit Smoking Among US Adults.

Importance: In 2006, a US district court judge ordered tobacco companies to sponsor nationwide antismoking advertising campaigns. This landmark ruling and its subsequent execution represent an unprecedented tobacco control event; however, the association of this campaign with intentions and/or attempts to quit smoking is unknown. Objectives: To assess the reach of the expanded court-ordered tobacco industry antismoking advertisements (via television, newspapers, tobacco company websites, and/or cigarette packages), to examine associations between exposure to industry antismoking advertisements and intentions and/or attempts to quit smoking among cigarette smokers, and to calculate the numbers of US smokers who would have quit intentions associated with exposure to multiple advertisements. Design, Setting, and Participants: Data for this study were obtained from 5309 US adults, including 610 smokers, who responded to the Health Information National Trends Survey, a nationally representative cross-sectional survey conducted from January 22 to April 30, 2019. Respondents were representatives of households selected by equal-probability sampling of a database of US residential addresses. Exposure: Reported exposure to antismoking messages. Main Outcomes and Measures: Cigarette smoking cessation attempt in the past 12 months and intentions to quit cigarette smoking in the next 6 months. Covariates were age, sex, household annual income, race/ethnicity, educational level, and geographical residence. Data were weighted to be nationally representative after applying survey weights specified for the survey cycle. Results: The overall sample of 5309 respondents were a mean (SD) age of 55.6 (19.1) years and included 3073 women (51.2%), 3037 non-Hispanic white respondents (59.1%), 4645 respondents who lived in urban US areas (84.7%), and 610 current smokers (12.5%). Findings indicate that 2464 US adults (45.8%; 95% CI, 43.2%-48.5%) and 410 current smokers (66.8%; 95% CI, 61.1%-72.4%) were exposed to antismoking advertisements. Exposure to multiple antismoking messages was associated with 2.19 (95% CI, 1.10-4.34) greater odds of having intentions to quit cigarette smoking but was not associated with attempts to quit (adjusted odds ratio, 1.31; 95% CI, 0.69-2.52). Furthermore, an examination of the association of cumulative exposure to antismoking messages with cessation intentions revealed that, with each additional exposure to an antismoking message, the odds of smoking cessation intentions increased by 1.21 (95% CI, 1.02-1.44). If all smokers were to be exposed to multiple antitobacco messages, there could be an estimated 3.98 million (95% CI, 492 480-7 223 040) current smokers in the United States with intentions to quit. Conclusions and Relevance: Although the reach of court-ordered industry advertisements increased among smokers, the reach of these advertisements within the general population remains suboptimal. The finding that industry advertisements helped smokers consider quitting highlights their potential to aid smoking cessation. However, the lack of association with actual attempts to quit suggests that the industry antismoking advertisement campaigns were inadequate. The design and content of industry antismoking advertisement campaigns should be enhanced to help smokers quit.

Reasons for not receiving the HPV vaccine among eligible adults: Lack of knowledge and of provider recommendations contribute more than safety and insurance concerns.

BACKGROUND: The upward trends of vaccine exemptions in Texas are alarming. While HPV vaccine rates in this State are among the lowest nationwide, factors that contribute to the low HPV vaccination uptake among adults remain unknown. In this study, we examined the main reasons for not receiving HPV vaccination among age-eligible adults. METHODS: The Texas health screening survey (2018), a multistage area probability design-based survey of a representative sample of Texas residents, was used to identify 907 eligible adults (age ≥ 18 years) respondents, including 724 women aged ≤ 26 years in 2007 (≤38 years in 2018), and 183 men aged ≤ 21 years in 2011 (≤28 years in 2018). Participants who reported having never received an HPV shot, where asked the main reason for not receiving the vaccine. RESULTS: Overall, 58.5% (95%CI: 55.1-62.0) of vaccine eligible adults reported having never received the HPV vaccine. The most commonly reported reasons for not receiving it were: did not know about the vaccine (18.5% (14.9-22.1)), and provider did not recommend (14.1% (10.9-17.4)). In contrast, commonly perceived reasons such as: safety concerns (7.2% (4.8-9.5)), lack of insurance (3.4% (1.7-5.1), and concerns about increasing sexual activity if vaccinated (0.2% (0.0-0.5)), were less frequently reported. CONCLUSION: Among vaccine-eligible adults, safety and sexuality concerns do not appear to be the prime factors underlying low HPV vaccination rates. Rather than emphasizing them, educational interventions should aim at improving vaccine's knowledge, and enhancing provider recommendations on the necessity of HPV vaccination.

Intracerebroventricular Infusion of Gangliosides Augments the Adult Neural Stem Cell Pool in Mouse Brain.

We previously reported that ganglioside GD3 is the predominant species in neural stem cells (NSCs) and reduced postnatal NSC pools are observed in both the subventricular zone and dentate gyrus (DG) of GD3-synthase knockout (GD3S-KO) mouse brains. Specifically, deficiency of GD3 in GD3S-KO animals revealed a dramatic reduction in cellularity in the DG of the hippocampus of the developing mouse brain, resulting in severe behavioral deficits in these animals. To further evaluate the functional role of GD3 in postnatal brain, we performed rescue experiments by intracerebroventricular infusion of ganglioside GD3 in adult GD3S-KO animals and found that it could restore the NSC pools and enhance the NSCs for self-renewal. Furthermore, 5xFAD mouse model was utilized, and GD3 restored NSC numbers and GM1 promoted neuronal differentiation. Our results thus demonstrate that exogenously administered gangliosides are capable to restore the function of postnatal NSCs. Since ganglioside expression profiles are associated not only with normal brain development but also with pathogenic mechanisms of diseases, such as Alzheimer's disease, we anticipate that the administration of exogenous gangliosides, such as GD3 and GM1, may represent a novel and effective strategy for promoting adult neurogenesis in damaged brain for disease treatment.

Prevalence and determinants of cervical cancer screening with a combination of cytology and human papillomavirus testing.

PURPOSE: In the United States, recommended options for cervical cancer screening in women aged 30 years or older include cytology alone or a combination of cytology and human papillomavirus (HPV) testing (co-testing). Although there is a body of evidence suggesting that co-testing may be the preferred screening option in this group of women, little is known about the characteristics of women who screen for cervical cancer with co-testing. METHODS: A multistage area probability design-based survey was administered to a representative sample of Texas residents. Of the 1348 female respondents, 572 women aged 30 years or older were included in this analysis. Population-weighted survey logistic regression was used to identify determinants of cervical screening with co-testing versus screening with cytology alone. RESULTS: Women vaccinated against HPV (aOR: 4.48, 95% CI: 1.25-15.97) or hepatitis B virus [aOR: 2.48 (1.52-4.02)], those with a personal cancer history [aOR: 2.96 (1.29-6.77)], and hormonal contraception users [aOR: 2.03 (1.03-3.97)] were more likely to be screened with co-testing than with cytology alone. Moreover, the likelihood of being screened with co-testing decreased with increasing age and decreasing annual household income. CONCLUSIONS: Benefits and indications of co-testing should be better explained to women and health care providers.