Effectiveness of Covid-19 Vaccines over a 9-Month Period in North Carolina.

BACKGROUND: The duration of protection afforded by coronavirus disease 2019 (Covid-19) vaccines in the United States is unclear. Whether the increase in postvaccination infections during the summer of 2021 was caused by declining immunity over time, the emergence of the B.1.617.2 (delta) variant, or both is unknown. METHODS: We extracted data regarding Covid-19-related vaccination and outcomes during a 9-month period (December 11, 2020, to September 8, 2021) for approximately 10.6 million North Carolina residents by linking data from the North Carolina Covid-19 Surveillance System and the Covid-19 Vaccine Management System. We used a Cox regression model to estimate the effectiveness of the BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and Ad26.COV2.S (Johnson & Johnson-Janssen) vaccines in reducing the current risks of Covid-19, hospitalization, and death, as a function of time elapsed since vaccination. RESULTS: For the two-dose regimens of messenger RNA (mRNA) vaccines BNT162b2 (30 µg per dose) and mRNA-1273 (100 µg per dose), vaccine effectiveness against Covid-19 was 94.5% (95% confidence interval [CI], 94.1 to 94.9) and 95.9% (95% CI, 95.5 to 96.2), respectively, at 2 months after the first dose and decreased to 66.6% (95% CI, 65.2 to 67.8) and 80.3% (95% CI, 79.3 to 81.2), respectively, at 7 months. Among early recipients of BNT162b2 and mRNA-1273, effectiveness decreased by approximately 15 and 10 percentage points, respectively, from mid-June to mid-July, when the delta variant became dominant. For the one-dose regimen of Ad26.COV2.S (5 × 1010 viral particles), effectiveness against Covid-19 was 74.8% (95% CI, 72.5 to 76.9) at 1 month and decreased to 59.4% (95% CI, 57.2 to 61.5) at 5 months. All three vaccines maintained better effectiveness in preventing hospitalization and death than in preventing infection over time, although the two mRNA vaccines provided higher levels of protection than Ad26.COV2.S. CONCLUSIONS: All three Covid-19 vaccines had durable effectiveness in reducing the risks of hospitalization and death. Waning protection against infection over time was due to both declining immunity and the emergence of the delta variant. (Funded by a Dennis Gillings Distinguished Professorship and the National Institutes of Health.).

Defining a vitamin A5/X specific deficiency - vitamin A5/X as a critical dietary factor for mental health.

A healthy and balanced diet is an important factor to assure a good functioning of the central and peripheral nervous system. Retinoid X receptor (RXR)-mediated signaling was identified as an important mechanism of transmitting major diet-dependent physiological and nutritional signaling such as the control of myelination and dopamine signalling. Recently, vitamin A5/X, mainly present in vegetables as provitamin A5/X, was identified as a new concept of a vitamin which functions as the nutritional precursor for enabling RXR-mediated signaling. The active form of vitamin A5/X, 9-cis-13,14-dehydroretinoic acid (9CDHRA), induces RXR-activation, thereby acting as the central switch for enabling various heterodimer-RXR-signaling cascades involving various partner heterodimers like the fatty acid and eicosanoid receptors/peroxisome proliferator-activated receptors (PPARs), the cholesterol receptors/liver X receptors (LXRs), the vitamin D receptor (VDR), and the vitamin A(1) receptors/retinoic acid receptors (RARs). Thus, nutritional supply of vitamin A5/X might be a general nutritional-dependent switch for enabling this large cascade of hormonal signaling pathways and thus appears important to guarantee an overall organism homeostasis. RXR-mediated signaling was shown to be dependent on vitamin A5/X with direct effects for beneficial physiological and neuro-protective functions mediated systemically or directly in the brain. In summary, through control of dopamine signaling, amyloid ß-clearance, neuro-protection and neuro-inflammation, the vitamin A5/X - RXR - RAR - vitamin A(1)-signaling might be "one of" or even "the" critical factor(s) necessary for good mental health, healthy brain aging, as well as for preventing drug addiction and prevention of a large array of nervous system diseases. Likewise, vitamin A5/X - RXR - non-RAR-dependent signaling relevant for myelination/re-myelination and phagocytosis/brain cleanup will contribute to such regulations too. In this review we discuss the basic scientific background, logical connections and nutritional/pharmacological expert recommendations for the nervous system especially considering the ageing brain.

Multi-nutrient interventions and cognitive ageing: are we barking up the right tree?

As we continue to elucidate the mechanisms underlying age-related brain diseases, the reductionist strategy in nutrition­brain function research has focused on establishing the impact of individual foods. However, the biological processes connecting diet and cognition are complex. Therefore, consideration of a combination of nutritional compounds may be most efficacious. One barrier to establishing the efficacy of multi-nutrient interventions is that the area lacks an established set of evidence-based guidelines for studying their effect on brain health. This review is an output of the International Life Sciences Institute (ILSI) Europe. A multi-disciplinary expert group was assembled with the aim of developing a set of considerations to guide research into the effects of multi-nutrient combinations on brain functions. Consensus recommendations converged on six key issues that should be considered to advance research in this area: (1) establish working mechanisms of the combination and contributions of each individual compound; (2) validate the relevance of the mechanisms for the targeted human condition; (3) include current nutrient status, intake or dietary pattern as inclusion/exclusion criteria in the study design; (4) select a participant population that is clinically and biologically appropriate for all nutritional components of the combination; (5) consider a range of cognitive outcomes; (6) consider the limits of reductionism and the 'gold standard' randomised controlled trial. These guiding principles will enhance our understanding of the interactive/complementary activities of dietary components, thereby strengthening the evidence base for recommendations aimed at delaying cognitive decline.

The role of interoception in age-related obesity: A structural equation modelling study.

The obesity pandemic and its adverse effect on health and quality of life are well established. In younger populations, interoception and aberrant eating behaviour contribute to overconsumption and being overweight. Although the incidence of obesity is higher in older individuals, they remain under-researched in the obesity literature. Therefore, the present study considered the role of general (interoceptive sensibility) and appetite-specific (hunger drive and satiety responsiveness) interoception and obesogenic eating behaviour (food responsivity, emotional eating, enjoyment of eating) in the association between age and BMI. A total of 1006 female adults (aged 18 to 80) completed the Adult Eating Behaviour Questionnaire and the Interoceptive Attention and Accuracy scales. Structural Equation Modelling (SEM) in AMOS was used to explore the data for multiple serial mediation effects. Despite being more overweight, older adults reported lower interoceptive attention, hunger drive, emotional overeating, food responsivity, and enjoyment of food. In contrast, compared to younger adults, older adults reported a higher interoceptive accuracy, and a similar responsivity to satiety. Importantly, two indirect pathways positively mediated the link between age and BMI: (1) age ➤(-)➤ interoceptive attention ➤(+)➤ satiety responsivity ➤(-)➤ emotional eating ➤(+)➤ BMI and (2) age ➤(-)➤ interoceptive attention ➤(+)➤ satiety responsivity ➤(-)➤ food responsivity ➤(+)➤ BMI. However, a stronger antagonistic indirect pathway was also present: age ➤(-)➤ interoceptive attention ➤(+)➤ hunger drive ➤(+)➤ emotional eating ➤(+)➤ BMI. The present findings suggested that overall reduced interoceptive attention in older adults may protect against weight gain by lowering hunger and the propensity towards obesogenic eating behaviours. These findings have implications for the design of appetite interventions in older populations.

Weaker connectivity in resting state networks is associated with disinhibited eating in older adults.

BACKGROUND/OBJECTIVES: Obesity affects more than forty percent of adults over the age of sixty. Aberrant eating styles such as disinhibition have been associated with the engagement of brain networks underlying executive functioning, attentional control, and interoception. However, these effects have been exclusively studied in young samples overlooking those most at risk of obesity related harm. METHODS: Here we assessed associations between resting-state functional connectivity and disinhibited eating (using the Three Factor Eating Questionnaire) in twenty-one younger (aged 19-34 years, BMI range: 18-31) and twenty older (aged 60-73 years, BMI range: 19-32) adults matched for BMI. The Alternative Healthy Eating Index was used to quantify diet quality. RESULTS: Older, compared to younger, individuals reported lower levels of disinhibited eating, consumed a healthier diet, and had weaker connectivity in the frontoparietal (FPN) and default mode (DMN) networks. In addition, associations between functional connectivity and eating behaviour differed between the two age groups. In older adults, disinhibited eating was associated with weaker connectivity in the FPN and DMN--effects that were absent in the younger sample. Importantly, these effects could not be explained by differences in habitual diet. CONCLUSIONS: These findings point to a change in interoceptive signalling as part of the ageing process, which may contribute to behavioural changes in energy intake, and highlight the importance of studying this under researched population.

Association of Primary and Booster Vaccination and Prior Infection With SARS-CoV-2 Infection and Severe COVID-19 Outcomes.

Importance: Data about the association of COVID-19 vaccination and prior SARS-CoV-2 infection with risk of SARS-CoV-2 infection and severe COVID-19 outcomes may guide prevention strategies. Objective: To estimate the time-varying association of primary and booster COVID-19 vaccination and prior SARS-CoV-2 infection with subsequent SARS-CoV-2 infection, hospitalization, and death. Design, Setting, and Participants: Cohort study of 10.6 million residents in North Carolina from March 2, 2020, through June 3, 2022. Exposures: COVID-19 primary vaccine series and boosters and prior SARS-CoV-2 infection. Main Outcomes and Measures: Rate ratio (RR) of SARS-CoV-2 infection and hazard ratio (HR) of COVID-19-related hospitalization and death. Results: The median age among the 10.6 million participants was 39 years; 51.3% were female, 71.5% were White, and 9.9% were Hispanic. As of June 3, 2022, 67% of participants had been vaccinated. There were 2 771 364 SARS-CoV-2 infections, with a hospitalization rate of 6.3% and mortality rate of 1.4%. The adjusted RR of the primary vaccine series compared with being unvaccinated against infection became 0.53 (95% CI, 0.52-0.53) for BNT162b2, 0.52 (95% CI, 0.51-0.53) for mRNA-1273, and 0.51 (95% CI, 0.50-0.53) for Ad26.COV2.S 10 months after the first dose, but the adjusted HR for hospitalization remained at 0.29 (95% CI, 0.24-0.35) for BNT162b2, 0.27 (95% CI, 0.23-0.32) for mRNA-1273, and 0.35 (95% CI, 0.29-0.42) for Ad26.COV2.S and the adjusted HR of death remained at 0.23 (95% CI, 0.17-0.29) for BNT162b2, 0.15 (95% CI, 0.11-0.20) for mRNA-1273, and 0.24 (95% CI, 0.19-0.31) for Ad26.COV2.S. For the BNT162b2 primary series, boosting in December 2021 with BNT162b2 had the adjusted RR relative to primary series of 0.39 (95% CI, 0.38-0.40) and boosting with mRNA-1273 had the adjusted RR of 0.32 (95% CI, 0.30-0.34) against infection after 1 month and boosting with BNT162b2 had the adjusted RR of 0.84 (95% CI, 0.82-0.86) and boosting with mRNA-1273 had the adjusted RR of 0.60 (95% CI, 0.57-0.62) after 3 months. Among all participants, the adjusted RR of Omicron infection compared with no prior infection was estimated at 0.23 (95% CI, 0.22-0.24) against infection, and the adjusted HRs were 0.10 (95% CI, 0.07-0.14) against hospitalization and 0.11 (95% CI, 0.08-0.15) against death after 4 months. Conclusions and Relevance: Receipt of primary COVID-19 vaccine series compared with being unvaccinated, receipt of boosters compared with primary vaccination, and prior infection compared with no prior infection were all significantly associated with lower risk of SARS-CoV-2 infection (including Omicron) and resulting hospitalization and death. The associated protection waned over time, especially against infection.

COVID-19 Vaccine Administration, by Race and Ethnicity - North Carolina, December 14, 2020-April 6, 2021.

COVID-19 has disproportionately affected non-Hispanic Black or African American (Black) and Hispanic persons in the United States (1,2). In North Carolina during January-September 2020, deaths from COVID-19 were 1.6 times higher among Black persons than among non-Hispanic White persons (3), and the rate of COVID-19 cases among Hispanic persons was 2.3 times higher than that among non-Hispanic persons (4). During December 14, 2020-April 6, 2021, the North Carolina Department of Health and Human Services (NCDHHS) monitored the proportion of Black and Hispanic persons* aged ≥16 years who received COVID-19 vaccinations, relative to the population proportions of these groups. On January 14, 2021, NCDHHS implemented a multipronged strategy to prioritize COVID-19 vaccinations among Black and Hispanic persons. This included mapping communities with larger population proportions of persons aged ≥65 years among these groups, increasing vaccine allocations to providers serving these communities, setting expectations that the share of vaccines administered to Black and Hispanic persons matched or exceeded population proportions, and facilitating community partnerships. From December 14, 2020-January 3, 2021 to March 29-April 6, 2021, the proportion of vaccines administered to Black persons increased from 9.2% to 18.7%, and the proportion administered to Hispanic persons increased from 3.9% to 9.9%, approaching the population proportion aged ≥16 years of these groups (22.3% and 8.0%, respectively). Vaccinating communities most affected by COVID-19 is a national priority (5). Public health officials could use U.S. Census tract-level mapping to guide vaccine allocation, promote shared accountability for equitable distribution of COVID-19 vaccines with vaccine providers through data sharing, and facilitate community partnerships to support vaccine access and promote equity in vaccine uptake.

Using engagement in sustainable construction to improve mental health and social connection in disadvantaged and hard to reach groups: a new green care approach.

Background: The positive impact of the outdoors on physical and mental health is increasingly being evidenced. However, the impact on vulnerable and disadvantaged individuals engaging in group based sustainable building construction has not been examined.Aim: To provide the first pragmatic examination of the impact of engaging in a brief (8 days over 8 weeks) outdoor sustainable construction project on the mental health and social connectedness of hard to reach and disadvantaged groups.Methods: In study 1, 93 young people not in education, employment or training took part whilst study 2 comprised 55 adults who were asylum seekers, long-term unemployed or men with longstanding depression. Self-report data were collected at baseline and towards the end of the programme.Results: Those with poor mental health and social connection at baseline showed statistically and clinically significant improvements in depression, anxiety, resilience and social connection by the end of the brief intervention.Conclusion: Engagement in a group based sustainable construction project can provide significant mental health and social benefits to a range of vulnerable and hard to reach groups with difficulties in these areas. Building on these findings could be important for health and social care policy for marginalised groups.

Interoceptive accuracy moderates the response to a glucose load: a test of the predictive coding framework.

Recently, interoception and homeostasis have been described in terms of predictive coding and active inference. Afferent signals update prior predictions about the state of the body, and stimulate the autonomic mediation of homeostasis. Performance on tests of interoceptive accuracy (IAc) may indicate an individual's ability to assign precision to interoceptive signals, thus determining the relative influence of ascending signals and the descending prior predictions. Accordingly, individuals with high IAc should be better able to regulate during the postprandial period. One hundred females were allocated to consume glucose, an artificially sweetened drink, water or no drink. Before, and 30 min after a drink, IAc, heart rate (HR) and blood glucose (BG) were measured, and participants rated their hunger, thirst and mood. A higher IAc was related to lower BG levels, a decline in anxiety and a higher HR, after consuming glucose. A higher IAc also resulted in a larger decline in hunger if they consumed either glucose or sucralose. These data support the role of active inference in interoception and homeostasis, and suggest that the ability to attend to interoceptive signals may be critical to the maintenance of physical and emotional health.

Heart-rate variability: a biomarker to study the influence of nutrition on physiological and psychological health?

As the influence of diet on health may take place over a period of decades, there is a need for biomarkers that help to identify those aspects of nutrition that have either a positive or a negative influence. The evidence is considered that heart-rate variability (HRV) (the time differences between one beat and the next) can be used to indicate the potential health benefits of food items. Reduced HRV is associated with the development of numerous conditions for example, diabetes, cardiovascular disease, inflammation, obesity and psychiatric disorders. Although more systematic research is required, various aspects of diet have been shown to benefit HRV acutely and in the longer term. Examples include a Mediterranean diet, omega-3 fatty acids, B-vitamins, probiotics, polyphenols and weight loss. Aspects of diet that are viewed as undesirable, for example high intakes of saturated or trans-fat and high glycaemic carbohydrates, have been found to reduce HRV. It is argued that the consistent relationship between HRV, health and morbidity supports the view that HRV has the potential to become a widely used biomarker when considering the influence of diet on mental and physical health.

Acute and repetitive fronto-cerebellar tDCS stimulation improves mood in non-depressed participants.

Transcranial direct current stimulation (tDCS) is a non-invasive form of brain stimulation, which allows for selective inhibition or excitation of neural structures. It has demonstrated some efficacy in the treatment of mood disorders. However, these studies have predominately focused on stimulation of the prefrontal cortex (PFC). The cerebellum has an increasingly recognized role in emotional control, affective state, and some psychopathologies. As such, tDCS research into mood modulation needs to expand beyond conventional PFC-focused paradigms. Using a contralateral stimulation electrode placement [anodal left dorsolateral(dl)PFC, cathodal right cerebellum], and a single-blind, repeated-measures design, we initially assessed changes in the mood of healthy participants in response to acute stimulation (n = 44) and three repeated stimulations delivered second-daily (n = 21). In a second experiment, we separately investigated the influence of reversed polarity upon these same measures, in response to acute stimulation (n = 23) and repeated stimulation (n = 11). We observed a systematic elevation of mood in both active conditions following single and repeated tDCS, the latter of which displayed a progressive elevation of mood from baseline. No mood change was noted in response to either single or repeated stimulation in the sham condition. Frontocerebellar tDCS stimulation advantageously influences mood in healthy participants, with an accumulative and potentiated effect following successive stimulations. The possibility that frontocerebellar stimulation may provide a novel therapeutic adjunctive or pre-emptive intervention in stress-related disorders and mood-related psychopathologies should be considered.

The effect of using isomaltulose (Palatinose™) to modulate the glycaemic properties of breakfast on the cognitive performance of children.

PURPOSE: Although previous research has associated the glycaemic load (GL) of a meal with cognitive functioning, typically the macro-nutrient composition of the meals has differed, raising a question as to whether the response was to GL or to the energy, nutrients or particular foods consumed. Therefore, the present study contrasted two breakfasts that offered identical levels of energy and macro-nutrients, although they differed in GL. METHODS: Using a repeated-measures, double-blind design, 75 children aged 5-11 years, from socially deprived backgrounds, attended a school breakfast club and on two occasions, at least a week apart, they consumed a meal sweetened with either isomaltulose (Palatinose™) (GL 31.6) or glucose (GL 59.8). Immediate and delayed verbal memory, spatial memory, sustained attention, reaction times, speed of information processing and mood were assessed 1 and 3 h after eating. RESULTS: The nature of the meals did not influence any measure of cognition or mood after an hour; however, after 3 h, children's memory and mood improved after the lower-GL breakfast. If children had eaten the lower-GL meal on the second day of testing, they were able to process information faster and had better spatial memory later in the morning. CONCLUSIONS: Towards the end of a morning in school, having consumed a lower-GL breakfast resulted in better mood and aspects of cognitive functioning.

The development of the predisposition to dehydration questionnaire.

The role played by hydration in general health and well-being is an emerging public health issue, yet there are few tools available to monitor its status in large populations. The aim was therefore to develop a questionnaire that assesses individual differences in the tendency to lose body fluid in a warm environment and hence become dehydrated. Fifty-three subjects sat in a room at 30°C for four hours and changes in mood and measures of hydration were monitored. There were marked individual differences in the loss of body mass that differed from 0.24% to 2.39%. Females who reported habitually drinking a lot had more water in their diet and at baseline the osmolality of urine was lower. After being subject to heat, those who reported habitually drinking more produced more urine, had a lower urine osmolality at the end of the study, and overall more body mass was lost. Females who reported that they responded badly to heat were more confused, unsure and depressed after four hours at 30°C. In males those reporting that they habitually drank to a greater extent had more water in the diet, and also those who dealt badly with heat habitually drank more. It was concluded that particularly in females, questionnaire measures were able to predict changes in hydration that result from a warm environment.

The UDP-diacylglucosamine pyrophosphohydrolase LpxH in lipid A biosynthesis utilizes Mn2+ cluster for catalysis.

In Escherichia coli and the majority of ß- and γ-proteobacteria, the fourth step of lipid A biosynthesis, i.e. cleavage of the pyrophosphate group of UDP-2,3-diacyl-GlcN, is carried out by LpxH. LpxH has been previously suggested to contain signature motifs found in the calcineurin-like phosphoesterase (CLP) family of metalloenzymes; however, it cleaves a pyrophosphate bond instead of a phosphoester bond, and its substrate contains nucleoside diphosphate moieties more common to the Nudix family rather than to the CLP family. Furthermore, the extent of biochemical data fails to demonstrate a significant level of metal activation in enzymatic assays, which is inconsistent with the behavior of a metalloenzyme. Here, we report cloning, purification, and detailed enzymatic characterization of Haemophilus influenzae LpxH (HiLpxH). HiLpxH shows over 600-fold stimulation of hydrolase activity in the presence of Mn(2+). EPR studies reveal the presence of a Mn(2+) cluster in LpxH. Finally, point mutants of residues in the conserved metal-binding motifs of the CLP family greatly inhibit HiLpxH activity, highlighting their importance in enzyme function. Contrary to previous analyses of LpxH, we find HiLpxH does not obey surface dilution kinetics. Overall, our work unambiguously establishes LpxH as a calcineurin-like phosphoesterase containing a Mn(2+) cluster coordinated by conserved residues. These results set the scene for further structural investigation of the enzyme and for design of novel antibiotics targeting lipid A biosynthesis.

The nature of the control of blood glucose in those with poorer glucose tolerance influences mood and cognition.

The ability to control the levels of blood glucose was related to mood and cognition. 155 adults, aged 45-85 years, without a diagnosis of diabetes, were given an oral glucose tolerance test and cognitive tests. Participants were classified according to age (41-60/61-85 years), whether they had better or poorer glucose tolerance and whether blood glucose did or did not fall below baseline values. There were two main findings. Those with poorer glucose tolerance forgot more words and had slower decision times, but only if 61 years or older. Secondly as there are reports in animal studies that inducing low levels of blood glucose values benefited cognitive performance, for the first time in humans, individual differences in the tendency to develop low levels of blood glucose were considered. In those with poor glucose tolerance a tendency for blood glucose to fall below baseline values was associated with better mood and faster working memory.

Early exposure to sugar sweetened beverages or fruit juice differentially influences adult adiposity.

OBJECTIVE: To examine associations between different types of sweet drinks consumed in early life and adult adiposity. DESIGN: The analysis involved the secondary analysis of the Avon Longitudinal Study of Parents and Children which followed children from birth to 24 years. Adiposity was measured using Dual-energy X-ray absorptiometry while food frequency questionnaires and diaries monitored diet. 'Early exposure' to sweet drinks was defined as giving a sugar-sweetened beverage or 100% fruit juice (FJ), before two years of age. RESULTS: Early exposure to cola was associated with higher fat mass, android fat mass and BMI at age 24 years; whereas early exposure to apple juice was associated with lower adult adiposity in females but not males. When age three, exposure to cola was associated with a greater intake of energy, carbohydrates, protein, fat, and less fruit and more fried foods. In contrast, early exposure to apple juice was associated with higher protein and lower fat intakes and consuming more fruits/vegetables and less fried foods. Parental education, adiposity and socio-economic status influenced whether SSB or FJ was given to a child. CONCLUSIONS: Early drinking of sugar sweetened beverages was associated with a less healthy dietary pattern, and greater adult adiposity. Early drinking of apple juice was associated with a healthier dietary pattern, and lower fat mass in adult females. The choice of drink was associated with social deprivation. As the dietary causes of adult obesity begin in early childhood, increased attention should be given to diet in the first years of life.