Recent Trends in the Incidence of Gastric Cancer in the United States.

BACKGROUND: Gastric cancer (GC) incidence rates overall in the United States have declined over recent decades and are predicted to continue declining. However, there have been mixed recent findings regarding the potential stabilization of rates and potential divergent trends by age group. We used the most recent cancer data for the United States and examined trends in GC between 1992 and 2019, overall and in important subgroups of the population. METHODS: Age-adjusted GC incidence rates and trends in adults 20 years or older were calculated using data from the Surveillance, Epidemiology, and End Results (SEER) 12 program. Secular trends were examined overall and by age group, sex, race/ethnicity, SEER registry, and tumor location. We used joinpoint regression to compute annual percent changes, average annual percent changes, and associated 95% CI. RESULTS: GC rates decreased by 1.23% annually from 1992 to 2019. Despite overall decreases, GC incidence rates increased for age groups below 50 years, predominately driven by noncardia GC (74.3% of all GCs). Cardia GC (26.7% of GC) rates decreased in all age groups except for 80 to 84 years. Overall GC rates decreased for both sexes, all races, and for all SEER registry regions, with the largest decreases occurring in males, Asians and Pacific Islanders, and in Hawaii. Age-period-cohort analysis revealed that birth cohorts before 1940 and after 1980 both had increased rates of GC compared with the reference birth cohort of 1955. CONCLUSION: GC rates overall have continued to decline through 2019, despite increases in the rate of noncardia GC for younger age groups.

Disparities in cancer mortality patterns: A comprehensive examination of U.S. rural and urban adults, 1999-2020.

BACKGROUND: Cancer mortality rates overall in the U.S. have decreased significantly; however, the rate of decline has not been uniform across sociodemographic groups. We aimed to compare trends in cancer mortality rates from 1999 to 2020 between rural and urban individuals and to examine whether any rural-urban differences are uniform across racial and ethnic groups. METHODS: We used U.S.-wide data from the National Center for Health Statistics, for all cancer deaths among individuals aged 25 years or older. We estimated average annual percentage change (AAPC) in age-standardized cancer mortality rates in the U.S. by cancer type, rural-urban status, sex, and race and ethnicity. RESULTS: There was a larger reduction in cancer mortality rates among individuals from urban (males: AAPC, -1.96%; 95% CI, -2.03, -1.90; females: AAPC, -1.56%; 95% CI, -1.64, -1.48) than rural (males: AAPC, -1.43%; 95% CI, -1.47, -1.39; females: AAPC, -0.93; 95% CI, -1.03, -0.82) areas. AAPCs for cancer types were uniformly higher among urban areas compared with rural areas. Despite overall decreases, deaths rates for liver and pancreas cancers increased, including in the most recent period among males (2012-2020, APC, 1.34; 95% CI, 0.49, 2.20) and females (2013-2020, APC, 1.52; 95% CI, 0.03, 3.02) in rural areas. CONCLUSIONS: Cancer death rates decreased in all racial and ethnic populations; however, the rural-urban differences varied by race/ethnicity. The rate of decline in mortality rates were lower in rural areas and death rates for liver and pancreas cancers increased, particularly for individuals living in rural America.

Burden of high-risk phenotype of heavy alcohol consumption among obese U.S. population: results from National Health and Nutrition Examination Survey, 1999-2020.

Background: The phenotype of combined heavy alcohol consumption and obesity has the potential to pose as a considerable health burden in the U.S. No studies using nationally representative data in the U.S. have reported their secular joint prevalence trends. We estimated the prevalence and examined the joint trends of heavy alcohol use and obesity over time among adult U.S. men and women in different age groups and according to race/ethnicity. Methods: Using data from 10 cycles of the U.S. National Health and Nutrition Examination Survey (NHANES) from 1999 to 2020, we examined secular trends in the combined phenotype of heavy drinking and obesity overall and by age-group, sex, and race/ethnicity. The main outcome measures were prevalence of heavy alcohol consumption (>14 drinks/week in men and >7 drinks/week in women) and obesity (BMI ≥30). Findings: In 45,292 adults (22,684 men, mean age 49.26 years; and 22,608 women, mean age 49.86), the overall weighted prevalence of combined heavy alcohol drinking and obesity increased from 1.8% (95% CI: 1.2%, 3.1%) in 1999-2000 to 3.1% (95% CI: 2.7%, 3.7%) in 2017-2020 representing an increase of 72% over time. In the joinpoint regression, the combined phenotype of heavy alcohol consumption and obesity increased by 3.25% (95% CI: 1.67%, 4.85%) per year overall from 1999 to 2017. An increasing trend of 9.94% (95% CI: 2.37%, 18.06%) per year was observed among adults aged between 40 and 59 years from 2007 onwards. Prevalence of heavy alcohol consumption in obesity increased at a faster rate among women (APC, 3.96%; 95% CI: 2.14%, 5.82%) than men (APC, 2.47%; 95% CI: 0.63%, 4.35%), and increased among non-Hispanic Whites (APC, 4.12%; 95% CI: 1.50%, 6.82%) and non-Hispanic Blacks (APC, 2.78%; 95% CI: 0.47%, 5.14%), but not Hispanics. Interpretation: The prevalence of combined heavy alcohol consumption and obesity increased overall in the U.S., but the rate of increase differed by age, sex, and race/ethnic groups. Given their independent and potential synergistic effects on premature mortality, public health policies on alcohol consumption need to reflect the background obesity epidemic. Funding: Cancer Prevention & Research Institute of Texas (CPRIT) for the Systems Epidemiology of Cancer Training (SECT) Program (RP210037; PI: A. Thrift).

Trends in Esophageal Adenocarcinoma and Esophageal Squamous Cell Carcinoma Incidence in the United States from 1992 to 2019.

BACKGROUND: Esophageal cancer (EC) incidence rates overall have declined in recent decades; however, the two main subtypes, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), show divergent secular trends. METHODS: Age-adjusted EC incidence rates were calculated using data from the Surveillance Epidemiology and End Results (SEER) 12 Program. We examined secular trends from 1992 to 2019 overall and by age group, sex, race/ethnicity, tumor location, and SEER registry. Joinpoint regression was used to compute annual percent changes (APC) and average annual percent changes (AAPC). We used age-period-cohort models to examine the potential impact of period and birth cohort effects on trends. RESULTS: Between 1992 and 2019, overall EC incidence rates declined by 0.54% annually (95% confidence interval [CI]: -0.75%, -0.33%). While ESCC rates declined linearly throughout the study period (AAPC = -2.85; 95%CI: -3.05%, -2.65%), EAC rates increased by over 5% annually from 1992 to 2000 (APC = 5.17; 95%CI: 3.28%, 7.10%), before stabilizing from 2000 to 2019 (APC = 0.22; 95%CI: -0.16%, 0.60%). Trends in ESCC and EAC varied by age group, sex, and race/ethnicity. Relative to ESCC rates among cohorts born circa 1950, the rates were 81% lower in cohorts born circa 1985 (rate ratio, 0.19; 95%CI: 0.04, 0.96). For EAC, rates have remained stable across successive birth cohorts since 1950. CONCLUSIONS: We observed linear declines in EC rates overall and for ESCC across age, sex, and race/ethnicity subgroups, but an inconsistent pattern for EAC. The trends in EAC cohorts born after 1955 were stable and suggest that EAC rates may have peaked in the U.S.

Increasing Incidence of Gallbladder Cancer among Non-Hispanic Blacks in the United States: A Birth Cohort Phenomenon.

BACKGROUND: Gallbladder cancer incidence varies among racial/ethnic subgroups in the United States (US). We investigated trends in gallbladder cancer incidence rates in 50 states from 2001 to 2018. METHODS: Age-adjusted incidence rates and trends in adults were calculated using data from the US Cancer Statistics registry. We used joinpoint regression to compute annual percentage of changes (APC). We analyzed incidence trends by time periods, age groups, and birth cohorts through age-period-cohort modeling. RESULTS: Overall, age standardized incidence rates for gallbladder cancer decreased by 0.3% annually between 2001 and 2018 [95% confidence interval (CI) -0.5% to -0.1%]. However, secular trends varied by race/ethnicity. Although gallbladder cancer rates declined in other racial/ethnic groups, rates increased by 1.4% annually among non-Hispanic Blacks (NHB) between 2001 and 2018 (APC = 1.4%; 95% CI, 0.9%-2.0%). We found evidence for period and birth cohort effects with increasing rates among successive birth cohorts of NHBs. Relative to NHB cohorts born circa 1946, gallbladder cancer rates were 85% higher in NHB cohorts born circa 1971 [incidence rate ratio (IRR), 1.85; 95% CI, 1.26-2.72). The rates among NHBs in South region were higher in cohorts born circa 1971 (IRR, 2.17; 95% CI, 1.27-3.73) relative to those born circa 1946. CONCLUSIONS: The incidence of gallbladder cancer has consistently increased in the US among NHBs. A notable increase in incidence was observed among NHBs with evidence of birth cohort effects in South, Northeast, and Midwest regions. IMPACT: The cohort effect observed among NHBs with increasing rates in different US regions suggests that gallbladder cancer rates will continue to rise in the US in the near future.

Predictors of COVID-19 perceived susceptibility: insights from population-based self-reported survey during lockdown in the United States.

BACKGROUND: The COVID-19 pandemic during lockdown has highlighted the importance of identifying individuals most at risk of infection with SARS-CoV-2, underscoring the need to assess factors contributing to susceptibility to disease. With the rapidly evolving nature of the pandemic and its new variants, there is an inadequate understanding on whether there are certain factors such as a specific symptom or collection of symptoms that combined with life-style behaviors may be useful to predict susceptibility. The study aims to explore such factors from pre-vaccination data to guide public health response to potential new waves. METHODS: An anonymous electronic survey was distributed through social media during the lockdown period in the United States from April to June 2020. Respondents were questioned regarding COVID testing, presenting symptoms, demographic information, comorbidities, and confirmation of COVID-19 test results. Stepwise logistic regression was used to identify predictors for COVID-19 perceived susceptibility. Selected classifiers were assessed for prediction performance using area under receiver operating characteristic (AUROC) curve analysis. RESULTS: A total of 130 participants deemed as susceptible because they self-reported their perception of having COVID-19 (but without the evidence of positive test) were compared with 130 individuals with documented negative test results. Participants had a mean age of 45 years, and 165 (63%) were female. Final multivariable model showed significant associations with perceived susceptibility for the following variables: fever (OR:33.5; 95%CI: 3.9,85.9), body ache (OR:3.0; 95%CI:1.1,6.4), contact history (OR:2.7; 95%CI:1.1,6.4), age> 50 (OR:2.7; 95%CI:1.1, 6.6) and smoking (OR:3.3; 95%CI: 1.2,9.1) after adjusting for other symptoms and presence of comorbid conditions. The AUROC ranged from poor to fair (0.65-0.76) for cluster of symptoms but improved to a good model (AUROC = 0.803) after inclusion of sociodemographic and lifestyle behaviors e.g., age and smoking tobacco. CONCLUSIONS: Fever and body aches suggest association with perceived COVID-19 susceptibility in the presence of demographic and lifestyle behaviors. Using other constitutional and respiratory symptoms with fever and body aches, the parsimonious classifier correctly predicts 80.3% of COVID-19 perceived susceptibility. A larger cohort of respondents will be needed to study and refine classifier performance in future lockdowns and with expected surge of new variants of COVID-19 pandemic.

Overcoming COVID-19 Vaccine Hesitancy: Insights from an Online Population-Based Survey in the United States.

This study sought to identify individual-level determinants of COVID-19 vaccine hesitancy based on the Health Belief Model (HBM) and Theory of Planned Behavior (TPB). An online population-based survey was distributed in English and Spanish. Data were derived from 1208 U.S. adults (52% female; 38.7% minorities), 43.5% of whom reported vaccine hesitancy. Multivariable analysis revealed that unemployed individuals were more likely (OR = 1.78, 95% CI: 1.16-2.73, p = 0.009) and married (OR = 0.57, 95% CI: 0.39-0.81, p = 0.002) and higher income individuals (OR = 0.52, 95% CI 0.32-0.84, p = 0.008) were less likely to be hesitant. Individuals with greater perceived susceptibility to COVID-19 (OR = 0.82, 95% CI: 0.71-0.94, p = 0.006), who perceived vaccination as being convenient (OR = 0.86, 95% CI: 0.74-1.00, p = 0.047), and who afforded greater importance to cues to action from government (OR = 0.84, 95% CI: 0.74-0.95, p = 0.005), public health (OR = 0.70, 95% CI: 0.59-0.82, p < 0.001), and healthcare experts (OR = 0.59, 95% CI: 0.50-0.69, p < 0.001) were also less likely to be hesitant. Findings suggest that HBM and TPB constructs may be useful in informing strategies to improve COVID-19 vaccine uptake. Specifically, framing appeals based on perceptions of COVID-19 susceptibility, making vaccination convenient, and rebuilding trust through unified cues to action may help to overcome vaccine hesitancy.

Sociodemographic and Health Belief Model Factors Associated with Nonadherence to COVID-19 Mitigation Strategies in the United States.

BACKGROUND AND PURPOSE: Virus mitigation strategies such as adhering to stay-at-home orders, practicing social distancing, and engaging in personal protective behaviors are central to slowing the spread of COVID-19. This population-based cohort study sought to identify sociodemographic characteristics and Health Belief Model factors that are associated with nonadherence to COVID-19 mitigation strategies with the goal of informing public health messaging campaigns. METHODS: An online population-based survey was distributed via social media over an 8-week period from April 13, 2020, to June 8, 2020. RESULTS: Data were derived from 2,222 adults (57% female; 40% racial/ethnic minorities). Univariate analyses revealed that men, younger aged (18-30 years) and unmarried adults, and noncollege educated individuals had lower levels of perceived threat, control, and knowledge about COVID-19 (p ≤ .001). Multivariable linear regression models further revealed that male gender was significantly associated with reporting lower levels of adherence to COVID-19 mitigation strategies (p < .001), and that higher levels of perceived threat, perceived control, and knowledge about how to keep oneself and others safe from COVID-19 were significantly associated with reporting higher levels of adherence to COVID-19 mitigation strategies (p < .01). CONCLUSIONS: Findings suggest that public health appeals that target men, emphasize individual risk, and provide clear, consistent guidance on what individuals can do to decrease their risk for COVID-19 may be effective in motivating increased mitigation adherence.

Individual-Level Determinants of Lifestyle Behavioral Changes during COVID-19 Lockdown in the United States: Results of an Online Survey.

This study examined individual-level determinants of self-reported changes in healthy (diet and physical activity) and addictive (alcohol use, smoking, and vaping) lifestyle behaviors during the initial COVID-19 lockdown period in the USA. A national online survey was administered between May and June 2020 that targeted a representative U.S. sample and yielded data from 1276 respondents, including 58% male and 50% racial/ethnic minorities. We used univariate and multivariable linear regression models to examine the associations of sociodemographic, mental health, and behavioral determinants with self-reported changes in lifestyle behaviors. Some study participants reported increases in healthy lifestyle behaviors since the pandemic (i.e., 36% increased healthy eating behaviors, and 33% increased physical activity). However, they also reported increases in addictive lifestyle behaviors including alcohol use (40%), tobacco use (41%), and vaping (46%). With regard to individual-level determinants, individuals who reported adhering to social distancing guidelines were also more likely to report increases in healthy lifestyle behaviors (ß = 0.12, 95% CI 0.04 to 0.21). Conversely, women (ß = -0.37, 95% CI -0.62 to -0.12), and unemployed individuals (ß = -0.33, 95% CI -0.64 to -0.02) were less likely to report increases in healthy lifestyle behaviors. In addition, individuals reporting anxiety were more likely to report increases in addictive behaviors (ß = 0.26, 95% CI 0.09 to 0.43). Taken together, these findings suggest that women and unemployed individuals may benefit from interventions targeting diet and physical activity, and that individuals reporting anxiety may benefit from interventions targeting smoking and alcohol cessation to address lifestyle changes during the pandemic.

Depletion of dietary phytoestrogens reduces hippocampal plasticity and contextual fear memory stability in adult male mouse.

Introduction: Phytoestrogens are non-steroidal estrogen analogues and are found primarily in soy products. They have received increasing attention as dietary supplements for estrogen deficiency and as modulators of endogenous estrogen functions, including cognition and emotion. In addition to modifying the levels of circulating sex hormones, phytoestrogens also exert direct effects on estrogen and androgen receptors in the brain and thus effectively modulate the neural circuit functions.Objective: The aim of this study was to investigate the long-term effects of low phytoestrogen intake (∼6 weeks) on the hippocampal plasticity and hippocampus-dependent memory formation in the adult C57BL/6 male mice.Methods and Results: In comparison to mice on a diet with normal phytoestrogen content, mice on low phytoestrogen diet showed a significant reduction in the phosphorylation of NR2B subunit, a molecular correlate of plasticity in the Schaffer collateral-CA1 synapse. We observed a profound decrease in long-term potentiation (LTP) in the ventral hippocampus, whereas no effect on plasticity was evident in its dorsal portion. Furthermore, we demonstrated that acute perfusion of slices with an estrogen analogue equol, an isoflovane metabolized from daidzein produced by the bacterial flora in the gut, was able to rescue the observed LTP deficit. Examining potential behavioral correlates of the plasticity attenuation, we found that mice on phytoestrogen-free diet display decreased contextual fear memory at remote but not at recent time points after training.Conclusions: Our data suggests that nutritional phytoestrogens have profound effects on the plasticity in the ventral hippocampus and ventral hippocampus-dependent memory.

Psychosocial and health behavioural impacts of COVID-19 pandemic on adults in the USA: protocol for a longitudinal cohort study.

INTRODUCTION: Although social distancing may help contain the spread of COVID-19, the social isolation and loneliness it causes can heighten stress, contribute to unhealthy lifestyle behaviours and have deleterious effects on social relationships. This ongoing longitudinal cohort study aims to (1) characterise the psychological, social and health behavioural impacts of the COVID-19 pandemic over a 12-month period in the USA; (2) determine whether these impacts differ for certain subgroups based on sociodemographics and other individual-level factors; and (3) explore whether there are modifiable factors (eg, coping, social support) that moderate the effects of the pandemic over time. METHODS AND ANALYSIS: Adults (aged ≥18 years) who were fluent in either English or Spanish were recruited via social media and invited to complete an online survey during the 8-week period from 13 April to 8 June 2020 (baseline). Follow-up surveys will be conducted 6 and 12 months after baseline. Data transformations, non-parametric tests or other alternative methods will be used when appropriate. Descriptive statistics and cross-sectional analyses will be performed. Longitudinal associations will be analysed using multilevel modelling with time-variant and time-invariant predictors of change in trajectory over the study period. ETHICS AND DISSEMINATION: Research ethics approval was received from the Baylor College of Medicine Institutional Review Board (H-47505). Overall, this study will provide timely information that can be used to inform public health messaging strategies and guide development of assessment tools and interventions to support vulnerable individuals dealing with the long-term impacts of the COVID-19 pandemic.

The association between use of opiates, cocaine, and amphetamines during pregnancy and maternal postpartum readmission in the United States: A retrospective analysis of the Nationwide Readmissions Database.

BACKGROUND: Substance use during pregnancy has increased in the United States, with adverse consequences for mother and baby. Similarly, postpartum readmission (PPR) imposes physical, emotional, and financial stressors causing disruption to family functioning and childcare. We used national data to estimate the extent to which women who used opiates, cocaine, and amphetamines during pregnancy are at increased risk of PPR. METHODS: We analyzed 2010-2014 data from the Nationwide Readmissions Database (NRD). Our exposure, drug use during pregnancy, was identified using diagnosis codes indicative of opioid, cocaine or amphetamine use, abuse, or dependence. The outcome was all-cause PPR, maternal readmission within 42 days following discharge from the delivery hospitalization. Multivariable logistic regression was used to estimate odds ratios (OR) that represented associations between drug use and PPR. RESULTS: Among 11 million delivery hospitalizations, nearly 1 % had documented use of opiates, cocaine and/or amphetamines. The crude PPR rate was nearly four times higher among users (54.6 per 1000) compared to non-users (14.0 per 1000), and 1 in 10 women who had documented use of more than one drug category experienced postpartum readmission. Even after controlling for sociodemographic and clinical confounders, we observed a two-fold increased odds of PPR among users compared to non-users (OR = 1.95; 95 % CI: 1.82, 2.07). CONCLUSIONS: The national opioid epidemic should encourage a paradigm shift in health care public policy to facilitate the management of all substance use disorders as chronic medical conditions through evidence-based public health initiatives to prevent these disorders, treat them, and promote recovery.

Estimating the obstetric co-morbidity burden using administrative data: The impact of the pregnancy-related assessment window.

BACKGROUND: Despite increased research using large administrative databases to identify determinants of maternal morbidity and mortality, the extent to which these databases capture obstetric co-morbidities is unknown. OBJECTIVE: To evaluate the impact that the time window used to assess obstetric co-morbidities has on the completeness of ascertainment of those co-morbidities. METHODS: We conducted a five-year analysis of inpatient hospitalisations of pregnant women from 2010-2014 using the Nationwide Readmissions Database. For each woman, using discharge diagnoses, we identified 24 conditions used to create the Obstetric Comorbidity Index. Using various assessment windows for capturing obstetric co-morbidities, including the delivery hospitalisation only and all weekly windows from 7 to 280 days, we calculated the frequency and rate of each co-morbidity and the degree of underascertainment of the co-morbidity. Under each scenario, and for each co-morbidity, we also calculated the all-cause, 30-day readmission rate. RESULTS: There were over 3 million delivery hospitalisations from 2010 to 2014 included in this analysis. Compared with a full 280-day window, assessment of obstetric co-morbidities using only diagnoses made during the delivery hospitalisation would result in failing to identify over 35% of cases of chronic renal disease, 28.5% cases in which alcohol abuse was documented during pregnancy, and 23.1% of women with pulmonary hypertension. For seven other co-morbidities, at least 1 in 20 women with that condition would have been missed with exclusive reliance on the delivery hospitalisation for co-morbidity diagnoses. Not only would reliance on delivery hospitalisations have resulted in missed cases of co-morbidities, but for many conditions, estimates of readmission rates for women with obstetric co-morbidities would have been underestimated. CONCLUSIONS: An increasing proportion of maternal and child health research is based on large administrative databases. This study provides data that facilitate the assessment of the degree to which important obstetric co-morbidities may be underascertained when using these databases.

SIPA1L2 controls trafficking and local signaling of TrkB-containing amphisomes at presynaptic terminals.

Amphisomes are organelles of the autophagy pathway that result from the fusion of autophagosomes with late endosomes. While biogenesis of autophagosomes and late endosomes occurs continuously at axon terminals, non-degradative roles of autophagy at boutons are barely described. Here, we show that in neurons BDNF/TrkB traffick in amphisomes that signal locally at presynaptic boutons during retrograde transport to the soma. This is orchestrated by the Rap GTPase-activating (RapGAP) protein SIPA1L2, which connects TrkB amphisomes to a dynein motor. The autophagosomal protein LC3 regulates RapGAP activity of SIPA1L2 and controls retrograde trafficking and local signaling of TrkB. Following induction of presynaptic plasticity, amphisomes dissociate from dynein at boutons enabling local signaling and promoting transmitter release. Accordingly, sipa1l2 knockout mice show impaired BDNF-dependent presynaptic plasticity. Taken together, the data suggest that in hippocampal neurons, TrkB-signaling endosomes are in fact amphisomes that during retrograde transport have local signaling capacity in the context of presynaptic plasticity.

Caldendrin Directly Couples Postsynaptic Calcium Signals to Actin Remodeling in Dendritic Spines.

Compartmentalization of calcium-dependent plasticity allows for rapid actin remodeling in dendritic spines. However, molecular mechanisms for the spatio-temporal regulation of filamentous actin (F-actin) dynamics by spinous Ca2+-transients are still poorly defined. We show that the postsynaptic Ca2+ sensor caldendrin orchestrates nano-domain actin dynamics that are essential for actin remodeling in the early phase of long-term potentiation (LTP). Steep elevation in spinous [Ca2+]i disrupts an intramolecular interaction of caldendrin and allows cortactin binding. The fast on and slow off rate of this interaction keeps cortactin in an active conformation, and protects F-actin at the spine base against cofilin-induced severing. Caldendrin gene knockout results in higher synaptic actin turnover, altered nanoscale organization of spinous F-actin, defects in structural spine plasticity, LTP, and hippocampus-dependent learning. Collectively, the data indicate that caldendrin-cortactin directly couple [Ca2+]i to preserve a minimal F-actin pool that is required for actin remodeling in the early phase of LTP.

Historical perspectives on prevention paradox: When the population moves as a whole.

Rose's Strategy of Preventive Medicine is critical reading for students and teachers in public health as well as practitioners of family and preventive medicine. In his classic, Geoffrey Rose outlines the prevention paradox that led to a discussion of two main preventive approaches to a disease, the individual- and population-based. This commentary briefly provides historical perspectives and viewpoints on the message of fundamental importance that when the population moves as a whole, the relative differences are the characteristics not of individuals but of populations. The "population as a whole" has been adopted in the lexicon of public health, enriched by Hippocrates' treatise on air, water, and places; Durkheim's collective consciousness; Pickering's continuous unimodal distribution; and Keys' charts of contrasting distributions. These readings should provide the public health professionals with a critical understanding of prevention paradox when they tend to focus only on the expression of the root cause above ground but fail to at the roots beneath the ground.

HIPP neurons in the dentate gyrus mediate the cholinergic modulation of background context memory salience.

Cholinergic neuromodulation in the hippocampus controls the salience of background context memory acquired in the presence of elemental stimuli predicting an aversive reinforcement. With pharmacogenetic inhibition we here demonstrate that hilar perforant path-associated (HIPP) cells of the dentate gyrus mediate the devaluation of background context memory during Pavlovian fear conditioning. The salience adjustment is sensitive to reduction of hilar neuropeptide Y (NPY) expression via dominant negative CREB expression in HIPP cells and to acute blockage of NPY-Y1 receptors in the dentate gyrus during conditioning. We show that NPY transmission and HIPP cell activity contribute to inhibitory effects of acetylcholine in the dentate gyrus and that M1 muscarinic receptors mediate the cholinergic activation of HIPP cells as well as their control of background context salience. Our data provide evidence for a peptidergic local circuit in the dentate gyrus that mediates the cholinergic encoding of background context salience during fear memory acquisition.Intra-hippocampal circuits are essential for associating a background context with behaviorally salient stimuli and involve cholinergic modulation at SST+ interneurons. Here the authors show that the salience of the background context memory is modulated through muscarinic activation of NPY+ hilar perforant path associated interneurons and NPY signaling in the dentate gyrus.