Evidence-Based Tools for Dietary Assessments in Nutrition Epidemiology Studies for Dementia Prevention

Increasing evidence proposes diet as a notable modifiable factor and viable target for the reduction of Alzheimer’s Disease risk and age-related cognitive decline. However, assessment of dietary exposures is challenged by dietary capture methods that are prone to misreporting and measurement errors. The utility of -omics technologies for the evaluation of dietary exposures has the potential to improve reliability and offer new insights to pre-disease indicators and preventive targets in cognitive aging and dementia. In this review, we present a focused overview of metabolomics as a validation tool and framework for investigating the immediate or cumulative effects of diet on cognitive health.

Application of the ARIMA Model to Predict Under-Reporting of New Cases of Hansen’s Disease during the COVID-19 Pandemic in a Municipality of the Amazon Region

This work aimed to apply the ARIMA model to predict the under-reporting of new Hansen’s disease cases during the COVID-19 pandemic in Palmas, Tocantins, Brazil. This is an ecological time series study of Hansen’s disease indicators in the city of Palmas between 2001 and 2020 using the autoregressive integrated moving averages method. Data from the Notifiable Injuries Information System and population estimates from the Brazilian Institute of Geography and Statistics were collected. A total of 7035 new reported cases of Hansen’s disease were analyzed. The ARIMA model (4,0,3) presented the lowest values for the two tested information criteria and was the one that best fit the data, as AIC = 431.30 and BIC = 462.28, using a statistical significance level of 0.05 and showing the differences between the predicted values and those recorded in the notifications, indicating a large number of under-reporting of Hansen’s disease new cases during the period from April to December 2020. The ARIMA model reported that 177% of new cases of Hansen’s disease were not reported in Palmas during the period of the COVID-19 pandemic in 2020. This study shows the need for the municipal control program to undertake immediate actions in terms of actively searching for cases and reducing their hidden prevalence.

Higher Serum BDNF Levels are Associated with Lower Risk of Cognitive Decline in Older Adults :The Otassha Study

Introduction There has been growing interest in the use of circulating levels of brain-derived neurotrophic factor (BDNF) in the blood as a biomarker in the context of patients with Alzheimer’s and other neurodegenerative diseases. Prospective data on cognitive decline in the broad older population, however, remain limited. We assessed the relationship of serum BDNF levels with short-term decline in cognitive functioning of community-dwelling older adults. Methods: Prospective study of 405 adults 65-84 years old without dementia in Tokyo, Japan. The Montreal Cognitive Assessment-Japanese version (MoCA-J) and its subscales were used. Linear regression assessed standardized differences in test score differences between baseline (2011) and follow-up (2013) visits, according to baseline serum BDNF quartiles, with adjustment for baseline demographics, disease indicators, and cognitive scores. Results Among participants who performed on the MoCA-J at baseline (scores in bottom quartile), cognitive decline was .65 (95% CI: .08 - 1.2; p=.025) standard deviations (SD) more pronounced in those with lowest than highest BDNF levels. Decline in executive function, but not in other subdomains, was also most pronounced in those with lowest baseline serum BDNF levels (difference: .32 SD; 95%CI: .08-.55; p=.007) Conclusion Lower serum BDNF levels were associated with greater 2-year cognitive decline in community-dwelling older Japanese adults. Decline varied among cognitive subdomains, and baseline cognition. Research seeking to evaluate the added-value of serum BDNF for screening and/or health promotion initiatives involving physical activity, which has been linked to increment in BDNF levels, is warranted.

Active syndromic surveillance of COVID-19 in Israel

Syndromic surveillance systems monitor disease indicators to detect emergence of diseases and track their progression. Here, we report on a rapidly deployed active syndromic surveillance system for tracking COVID-19 in Israel. The system was a novel combination of active and passive components: Ads were shown to people searching for COVID-19 symptoms on the Google search engine. Those who clicked on the ads were referred to a chat bot which helped them decide whether they needed urgent medical care. Through its conversion optimization mechanism, the ad system was guided to focus on those people who required such care. Over 6 months, the ads were shown approximately 214,000 times and clicked on 12,000 times, and 722 people were informed they needed urgent care. Click rates on ads and the fraction of people deemed to require urgent care were correlated with the hospitalization rate ($$R^2=0.54$$ R 2 = 0.54 and $$R^2=0.50$$ R 2 = 0.50 , respectively) with a lead time of 9 days. Males and younger people were more likely to use the system, and younger people were more likely to be determined to require urgent care (slope: $$- \,0.009$$ - 0.009 , $$P=0.01$$ P = 0.01 ). Thus, the system can assist in predicting case numbers and hospital load at a significant lead time and, simultaneously, help people determine if they need medical care.

Intake of Flavonoids and Odds of Frailty Onset in Adults in the Framingham Offspring Cohort

Polyphenols (antioxidants derived from plant-foods) could play a role in inhibition of oxidative stress and frailty reduction, yet data on the polyphenol subclass of dietary flavonoids is limited. This study sought to determine the association between dietary flavonoids and frailty onset in middle-aged and older adults. This prospective cohort study included non-frail individuals from the Framingham Offspring Cohort (FOC) with total flavonoid intake (mg/day; defined as sum flavonols, flavan-3-ols, flavonones, flavones, and anthocyanins via Harvard Food Frequency Questionnaire), frailty (via Fried phenotype), and covariate information measured at baseline (1998-2001). Follow-up frailty was evaluated in 2011-2014. Logistic regression estimated odds ratio (OR) and 95% confidence intervals (95% CI) adjusting for relevant confounders. Participants (n=1,701; 55.5% female) had a mean age of 58.4 years (SD ± 8.3). Mean flavonoid intake was 309 mg/d (SD ± 266). After 12.4 years (SD ± 0.8), 224 (13.2%) individuals exhibited frailty. In age and sex adjusted models, every 50 mg/day of higher total flavonoid intake was associated with 3% reduced odds of frailty [OR (95%CI): 0.97 (0.94-1.00), p-value: 0.05). Further adjustment for smoking, energy and protein intake, and disease indicators did not appreciably change the association, and associations became non-significant (p-value=0.12). Thus, there was no association between flavonoid intake and odds of frailty onset in adults in the FOC. This could be due to participants' higher intake of flavonoids compared to average intake of ~200 mg/d in Americans.

Prognostic Role and Diagnostic Power of Seven Indicators in COVID-19 Patients

The prognostic role and diagnostic ability of coronavirus disease 2019 (COVID-19) disease indicators are not elucidated, thus, the current study aimed to investigate the prognostic role and diagnostic ability of several COVID-19 disease indicators including the levels of oxygen saturation, leukocytes, lymphocytes, albumin, C-reactive protein (CRP), interleukin-6 (IL-6), and D-dimer in patients with COVID-19. The levels of oxygen saturation, lymphocytes, and albumin were significantly higher in the common and severe clinical type patients compared with those in critical type patients. However, levels of leukocytes, CRP, IL-6, and D-dimer were significantly lower in the common and severe type patients compared with those in critical type patients (P < 0.001). Moreover, the current study demonstrated that the seven indicators have good diagnostic and prognostic powers in patients with COVID-19. Furthermore, a two-indicator (CRP and D-dimer) prognostic signature in training and testing datasets was constructed and validated to better understand the prognostic role of the indicators in COVID-19 patients. The patients were classified into high-risk and low-risk groups based on the median-risk scores. The findings of the Kaplan–Meier curve analysis indicated a significant divergence between the high-risk and low-risk groups. The findings of the receiver operating curve (ROC) analysis indicated the good performance of the signature in the prognosis prediction of COVID-19. In addition, a nomogram was constructed to assist clinicians in developing clinical decision-making for COVID-19 patients. In conclusion, the findings of the current study demonstrated that the seven indicators are potential diagnostic markers for COVID-19 and a two-indicator prognostic signature identification may improve clinical management for COVID-19 patients.

A Novel OGR1 (GPR68) Inhibitor Attenuates Inflammation in Murine Models of Colitis

<b><i>Background and Aims:</i></b> Local extracellular acidification is associated with several conditions, such as ischemia, cancer, metabolic disease, respiratory diseases, and inflammatory bowel disease (IBD). Several recent studies reported a link between IBD and a family of pH-sensing G protein-coupled receptors. Our previous studies point to an essential role for OGR1 (GPR68) in the modulation of intestinal inflammation and fibrosis. In the current study, we evaluated the effects of a novel OGR1 inhibitor in murine models of colitis. <b><i>Methods:</i></b> The effects of a novel small-molecule OGR1 inhibitor were assessed in the acute and chronic dextran sulfate sodium (DSS) murine models of colitis. Macroscopic disease indicators of intestinal inflammation were evaluated, and epithelial damage and immune cell infiltration and proliferation were assessed by immunohistochemistry. <b><i>Results:</i></b> The OGR1 inhibitor ameliorated clinical parameters in acute and chronic DSS-induced colitis. In mice treated with the OGR1 inhibitor, endoscopy showed no thickening and normal vascularity, while fibrin was not detected. Histopathological findings revealed a decrease in severity of colonic inflammation in the OGR1 inhibitor group when compared to vehicle-DSS controls. In OGR1 inhibitor-treated mice, staining for the macrophage marker F4/80 and cellular proliferation marker Ki-67 revealed a reduction of infiltrating macrophages and slightly enhanced cell proliferation, respectively. This was accompanied by a reduction in pro-inflammatory cytokines, TNF and IL-6, and the fibrosis marker TGF-β1. <b><i>Conclusion:</i></b> This is the first report providing evidence that a pharmacological inhibition of OGR1 has a therapeutic effect in murine colitis models. Our data suggest that targeting proton-sensing OGR1 using specific small-molecule inhibitors may be a novel therapeutic approach for the treatment of IBD.

Bacterial Community Changes in Penaeus vannamei Boone, 1931 Surface and Rearing Water During Enterocytozoon hepatopenaei Infection

White faeces syndrome is one of the major disease problems in shrimp aquaculture, resulting in enormous economic losses to farmers. Although white faeces syndrome is usually associated with Enterocytozoon hepatopenaei (EHP) infections, it may not be the sole cause for the occurrence of white faecal strings on the pond water surface. There is limited information on the microbial dynamics in a pond affected by white faeces syndrome. Hence, this study aimed at the bacterial community changes occurring on the surface of shrimp Penaeus vannamei Boone, 1931 afflicted by the white faeces syndrome and the pond water in which it was reared. The pond water and the shrimp surface shared >45 % of the operational taxonomic units (OTUs), reflecting the influence of water quality on the bacterial community composition on the shrimp surface. Among these, the Proteobacteria formed the principal phyla and remained unaltered throughout the culture period. Bacteroidetes formed the second largest group across samples, followed by Cyanobacteria, Actinobacteria, Planctomycetes, Verrucomicrobia and Chloroflexi. The relative abundance levels of health indicator bacterial families such as Thiotrichaceae,Microbacteriaceae and Chitinophagaceae showed significant fluctuations on the shrimp surface. Disease indicators such as Rickettsiaceae, Mycobacteriaceae showed an increase in numbers on the shrimp surface. PICRUSt functional predictions revealed higher abundances of genes involved in metabolism and genetic information processing. The study provides valuable findings on the bacterial communities of rearing water and shrimp surface associated with white faeces syndrome.

Ablation of kynurenine 3-monooxygenase rescues plasma inflammatory cytokine levels in the R6/2 mouse model of Huntington’s disease

Kynurenine 3-monooxygenase (KMO) regulates the levels of neuroactive metabolites in the kynurenine pathway (KP), dysregulation of which is associated with Huntington’s disease (HD) pathogenesis. KMO inhibition leads to increased levels of neuroprotective relative to neurotoxic metabolites, and has been found to ameliorate disease-relevant phenotypes in several HD models. Here, we crossed KMO knockout mice to R6/2 HD mice to examine the effect of KMO depletion in the brain and periphery. KP genes were dysregulated in peripheral tissues from R6/2 mice and KMO ablation normalised levels of a subset of these. KP metabolites were also assessed, and KMO depletion led to increased levels of neuroprotective kynurenic acid in brain and periphery, and dramatically reduced neurotoxic 3-hydroxykunurenine levels in striatum and cortex. Notably, the increased levels of pro-inflammatory cytokines TNFa, IL1β, IL4 and IL6 found in R6/2 plasma were normalised upon KMO deletion. Despite these improvements in KP dysregulation and peripheral inflammation, KMO ablation had no effect upon several behavioural phenotypes. Therefore, although genetic inhibition of KMO in R6/2 mice modulates several metabolic and inflammatory parameters, these do not translate to improvements in primary disease indicators—observations which will likely be relevant for other interventions targeted at peripheral inflammation in HD.