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The mutation profile of the SARS-CoV-2 Omicron (lineage BA.1) variant posed a concern for naturally acquired and vaccine-induced immunity. We investigated the ability of prior infection with an early SARS-CoV-2 ancestral isolate (Australia/VIC01/2020, VIC01) to protect against disease caused by BA.1. We established that BA.1 infection in naïve Syrian hamsters resulted in a less severe disease than a comparable dose of the ancestral virus, with fewer clinical signs including less weight loss. We present data to show that these clinical observations were almost absent in convalescent hamsters challenged with the same dose of BA.1 50 days after an initial infection with ancestral virus. These data provide evidence that convalescent immunity against ancestral SARS-CoV-2 is protective against BA.1 in the Syrian hamster model of infection. Comparison with published pre-clinical and clinical data supports consistency of the model and its predictive value for the outcome in humans. Further, the ability to detect protection against the less severe disease caused by BA.1 demonstrates continued value of the Syrian hamster model for evaluation of BA.1-specific countermeasures.

Lambe, Spencer, Thomas, Gilbert and colleagues report on the detailed immune profile of rhesus macaques and ferrets vaccinated against SARS-CoV-2 under high dose challenge. Their findings indicate that the ChAdOx1 nCoV-19 (AZD1222) the vaccine induces immune responses and reduces disease symptoms in both models, including SARS-CoV-2 mediated pneumonia and virus shedding.

Non-human primates are important animal models for studying SARS-CoV-2 infection. Here, Salguero et al. directly compare rhesus and cynomolgus macaques and show that both species represent COVID-19 disease of mild clinical cases, and provide a lung histopathology scoring system.

SARS-CoV-2 induces mild infection in ferret model. Here, Ryan et al. characterise optimal infection dosage inducing upper respiratory tract (UTR) viral shedding, progression time of viral shedding, and pathology in ferrets and finally provide evidence for protection after re-challenge.

Background: The novel human coronavirus SARS-CoV-2 is a major ongoing global threat with huge economic burden. Like all respiratory viruses, SARS-CoV-2 initiates infection in the upper respiratory tract (URT). Infected individuals are often asymptomatic, yet highly infectious and readily transmit virus. A therapy that restricts initial replication in the URT has the potential to prevent progression of severe lower respiratory tract disease as well as limiting person-to-person transmission. Methods: SARS-CoV-2 Victoria/01/2020 was passaged in Vero/hSLAM cells and virus titre determined by plaque assay. Challenge virus was delivered by intranasal instillation to female ferrets at 5.0 × 106 pfu/ml. Treatment groups received intranasal INNA-051, developed by Ena Respiratory. SARS-CoV-2 RNA was detected using the 2019-nCoV CDC RUO Kit and QuantStudio™ 7 Flex Real-Time PCR System. Histopathological analysis was performed using cut tissues stained with haematoxylin and eosin (H&E). Findings: We show that prophylactic intra-nasal administration of the TLR2/6 agonist INNA-051 in a SARS-CoV-2 ferret infection model effectively reduces levels of viral RNA in the nose and throat. After 5 days post-exposure to SARS-CoV-2, INNA-051 significantly reduced virus in throat swabs (p=

Despite high vaccination coverage, Bordetella pertussis the causative agent of whooping cough is still a health concern worldwide. A resurgence of pertussis cases has been reported, particularly in countries using acellular vaccines with waning immunity and pathogen adaptation thought to be responsible. A better understanding of protective immune responses is needed for the development of improved vaccines. In our study, B. pertussis strain B1917 variants presenting a single gene deletion were generated to analyze the role of vaccine components or candidate vaccine antigens as targets for bactericidal antibodies generated after acellular vaccination or natural infection. Our results show that acellular vaccination generates bactericidal antibodies that are only directed against pertactin. Serum bactericidal assay performed with convalescent samples show that disease induces bactericidal antibodies against Prn but against other antigen(s) as well. Four candidate vaccine antigens (CyaA, Vag8, BrkA, and TcfA) have been studied but were not targets for complement-mediated bactericidal antibodies after natural infection. We confirm that Vag8 and BrkA are involved in complement resistance and would be targeted by blocking antibodies. Our study suggests that the emergence and the widespread circulation of Prn-deficient strains is driven by acellular vaccination and the generation of bactericidal antibodies targeting Prn.

The mutation profile of the SARS-CoV-2 Omicron (lineage BA.1) variant posed a concern for naturally acquired and vaccine-induced immunity. We investigated the ability of prior infection with an early SARS-CoV-2 ancestral isolate (Australia/VIC01/2020, VIC01) to protect against disease caused by BA.1. We established that BA.1 infection in naïve Syrian hamsters resulted in a less severe disease than a comparable dose of the ancestral virus, with fewer clinical signs including less weight loss. We present data to show that these clinical observations were almost absent in convalescent hamsters challenged with the same dose of BA.1 50 days after an initial infection with ancestral virus. These data provide evidence that convalescent immunity against ancestral SARS-CoV-2 is protective against BA.1 in the Syrian hamster model of infection. Comparison with published pre-clinical and clinical data supports consistency of the model and its predictive value for the outcome in humans. Further, the ability to detect protection against the less severe disease caused by BA.1 demonstrates continued value of the Syrian hamster model for evaluation of BA.1-specific countermeasures. Author summary: The Golden Syrian hamster model has proved to be a robust model for SARS-CoV-2, with clinical signs, pathological changes and viral load outputs providing endpoints for an animal model of COVID-19, suitable for the assessment of interventions that may serve to prevent infection, transmission and/or disease. Following wild type virus infection in the hamster model there is robust, lasting immunity and protection upon rechallenge making studying breakthrough infection difficult. The initial purpose of this study is to monitor for waning immunity in the hamster model and characterise at what timepoint breakthrough infection might occur when rechallenged. When the Omicron variant emerged in November 2021 the opportunity was taken to assess the Omicron variant in the hamster model. Here we show that at 50 days following ancestral SARS-CoV-2 infection hamsters are well protected from Omicron rechallenge, and although Omicron infection is mild in hamsters we could discriminate well between protected and unprotected hamsters. [ABSTRACT FROM AUTHOR]

Aims: To measure the prevalence of visual impairment in a large representative sample of people aged 75 years and over participating in the MRC trial of assessment and management of [...]

Despite high vaccination coverage, Bordetella pertussis the causative agent of whooping cough is still a health concern worldwide. A resurgence of pertussis cases has been reported, particularly in countries using acellular vaccines with waning immunity and pathogen adaptation thought to be responsible. A better understanding of protective immune responses is needed for the development of improved vaccines. In our study, B. pertussis strain B1917 variants presenting a single gene deletion were generated to analyze the role of vaccine components or candidate vaccine antigens as targets for bactericidal antibodies generated after acellular vaccination or natural infection. Our results show that acellular vaccination generates bactericidal antibodies that are only directed against pertactin. Serum bactericidal assay performed with convalescent samples show that disease induces bactericidal antibodies against Prn but against other antigen(s) as well. Four candidate vaccine antigens (CyaA, Vag8, BrkA, and TcfA) have been studied but were not targets for complement-mediated bactericidal antibodies after natural infection. We confirm that Vag8 and BrkA are involved in complement resistance and would be targeted by blocking antibodies. Our study suggests that the emergence and the widespread circulation of Prn-deficient strains is driven by acellular vaccination and the generation of bactericidal antibodies targeting Prn. [ABSTRACT FROM AUTHOR]

Dietary intake of isothiocyanates (ITC) has been associated with reduced cancer risk. The dietary phenethyl ITC (PEITC) has previously been shown to decrease the phosphorylation of the translation regulator 4E binding protein 1 (4E-BP1). Decreased 4E-BP1 phosphorylation has been linked to the inhibition of cancer cell survival and decreased activity of the transcription factor hypoxia-inducible factor (HIF), a key positive regulator of angiogenesis, and may therefore contribute to potential anti-cancer effects of PEITC. In the present study, we have investigated the in vitro and in vivo effects of watercress, which is a rich source of PEITC. We first demonstrated that, similar to PEITC, crude watercress extracts inhibited cancer cell growth and HIF activity in vitro. To examine the effects of dietary intake of watercress, we obtained plasma and peripheral blood mononuclear cells following the ingestion of an 80 g portion of watercress from healthy participants who had previously been treated for breast cancer. Analysis of PEITC in plasma samples from nine participants demonstrated a mean maximum plasma concentration of 297 nm following the ingestion of watercress. Flow cytometric analysis of 4E-BP1 phosphorylation in peripheral blood cells from four participants demonstrated significantly reduced 4E-BP1 phosphorylation at 6 and 8 h following the ingestion of watercress. Although further investigations with larger numbers of participants are required to confirm these findings, this pilot study suggests that flow cytometry may be a suitable approach to measure changes in 4E-BP1 phosphorylation following the ingestion of watercress, and that dietary intake of watercress may be sufficient to modulate this potential anti-cancer pathway. [ABSTRACT FROM PUBLISHER]

Leaf senescence is an active process that involves the increased expression of many hundreds of genes. Many putative transcription factors show enhanced transcription during leaf senescence in Arabidopsis and functional analysis of these should help to indicate their role in controlling gene expression during leaf senescence. In this paper, we describe the analysis of knockout insertion mutants in two different senescence-enhanced genes, one encodes a heat shock transcription factor and the other a zinc finger protein. Plants mutated in these genes show accelerated leaf senescence and reduced tolerance to drought stress, indicating that expression of these genes during senescence has a protective role to maintain viability during this essential developmental process. Analysis of gene expression changes in both mutants compared to the wild-type plants indicates an increased rate of senescence but does not show clearly the pathway that is dependent on these genes for expression. The complexities of signalling networks in plant stress and the plasticity of plant responses mean that the direct consequences of mutation are very difficult to define. The usefulness of this type of approach to address the burning question of how senescence is regulated is discussed, and an alternative approach aimed at a more global analysis of gene regulation using systems biology methods is described. [ABSTRACT FROM AUTHOR]

Background: Guidelines for optimal weight in older persons are limited by uncertainty about the ideal body mass index (BMI) or the usefulness of alternative anthropometric measures. Objective: We investigated the association of BMI (in kg/m[2]), waist circumference, and waist-hip ratio (WHR) with mortality and cause-specific mortality. Design: Subjects aged >/=75 y (n = 14 833) from 53 family practices in the United Kingdom underwent a health assessment that included measurement of BMI and waist and hip circumferences; they also were followed up for mortality. Results: During a median follow-up of 5.9 y, 6649 subjects died (46% of circulatory causes). In nonsmoking men and women (90% of the cohort), compared with the lowest quintile of BMI (<23 in men and <22.3 in women), adjusted hazard ratios (HRs) for mortality were <1 for all other quintiles of BMI (P for trend = 0.0003 and 0.0001 in men and women, respectively). Increasing WHR was associated with increasing HRs in men and women (P for trend = 0.008 and 0.0002, respectively). BMI was not associated with circulatory mortality in men (P for trend = 0.667) and was negatively associated in women (P for trend = 0.004). WHR was positively related to circulatory mortality in both men and women (P for trend = 0.001 and 0.005, respectively). Waist circumference was not associated with all-cause or circulatory mortality. Conclusions: Current guidelines for BMI-based risk categories overestimate risks due to excess weight in persons aged >/=75 y. Increased mortality risk is more clearly indicated for relative abdominal obesity as measured by high WHR. © 2006 American Society for Nutrition [ABSTRACT FROM AUTHOR]

BACKGROUND: Older persons are at risk of both poor nutrition and increased oxidative stress. Plasma ascorbate concentrations fall with increasing age, and concentrations of other antioxidants may also be reduced. OBJECTIVE: The goal was to examine the association between antioxidants and mortality in older persons. DESIGN: We randomly selected persons aged 75-84 y from the lists of 51 British family practitioners taking part in a randomized trial of assessment of older persons. A total of 1214 participants provided a blood sample and were interviewed about their usual diet with the use of a food-frequency questionnaire. Statistical analyses were based on deaths after a median of 4.4 y of follow-up, and hazard ratios were estimated for quintiles of dietary or blood antioxidants. RESULTS: We found strong inverse trends for blood ascorbate concentrations with all-cause and cardiovascular disease mortality, which were only marginally reduced after adjustment for confounders or supplement use. Those in the lowest fifth (< 17 micromol/L) had the highest mortality, whereas those in the highest fifth (> 66 micromol/L) had a mortality risk nearly half that (hazard ratio = 0.54; 95% CI: 0.34, 0.84). Similar results were found after the exclusion of those subjects with cardiovascular disease or cancer at baseline (hazard ratio = 0.51; 0.28, 0.93). In fully adjusted models, there was no evidence for an influence of alpha-tocopherol, beta-carotene, or retinol on total mortality. Dietary antioxidants measured by the food-frequency questionnaire were not associated with all-cause or cardiovascular disease mortality. CONCLUSION: Low blood vitamin C concentrations in the older British population are strongly predictive of mortality. Copyright © 2003 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study examined (1) the relation of employment grade in middle age to self-reported poor health and functional limitations in old age and (2) whether socioeconomic status at approximately the time of retirement modifies health differentials in old age. METHODS: Survivors of the Whitehall Study cohort of men were resurveyed. Respondents were aged 40 to 69 years when they were originally screened in 1967 to 1970. RESULTS: Compared with senior administrators, men in clerical or manual (low-grade) jobs in middle age had quadruple the odds of poor physical performance in old age, triple the odds of poor general health, and double the odds of poor mental health and disability. At most, 20% of these differences were explained by baseline health or risk factors. Men who moved from low to middle grades before retirement were less likely than those who remained in low grades to have poor mental health. CONCLUSIONS: Socioeconomic status in middle age and at approximately retirement age is associated with morbidity in old age. © 2002 by the United States Cancer Pain Relief Committee. [ABSTRACT FROM AUTHOR]

Background: In the light of increasing interest in health inequalities, this paper aims to assess i) whether material deprivation in late middle age and early old age is associated with greater risk of limiting long-term illness 20 years later and ii) whether deterioration in socioeconomic status during the first 10 years carries a higher risk than remaining in a higher status. Methods: The Longitudinal Study comprised a 1% sample of people registered on the 1971 Census in England and Wales; data from successive censuses are linked with vital events such as deaths. The subjects were 23,320 people aged 55-74 years in 1971 and living in the community in 1971, 1981 and 1991. Logistic regression was used to perform the analyses. Results: The relative risk of having a limiting long-term illness 20 years later for people in rented accommodation without a car at age 55-64 years was 1.2 compared to those in owner-occupied accommodation with a car. For those aged 65-74 years in 1971 the excess risk was 9%. Moving out of owner occupation between 1971 and 1981 and losing access to a car were associated with excess risk similar to that for people already disadvantaged in 1971. Thus, socioeconomic circumstances in late middle and early old age and deterioration in such circumstances after age 55 years, are associated with limiting long-term illness among people who have survived in the community until at least age 75 years. Conclusion: Although health selection cannot be ruled out, it appears that health inequalities do not completely disappear in very old age. [ABSTRACT FROM AUTHOR]

To identify socioeconomic and demographic predictors of long term mortality and institutional residence in old age, taking into account changes in socioeconomic and demographic circumstances between the 1971 and 1981 censuses. Multivariate logistic regression modelling of outcomes for 10 year age cohorts of each gender. The outcomes were death by 31 December 1992; being in an institution in 1991. Members of the Longitudinal Study (a 1% sample of the British Census): 43,092 men and 50,839 women aged 55-74 in 1971. Being in rented accommodation and in a household without access to a car carried 35-45% higher mortality rate over 21 years and similar excess risk of being in an institution in 1991. Marital status and living arrangements were weaker predictors of death but being single was a major predictor of moving to an institution for men. Losing household access to a car was a strong factor for mortality for men and for institutionalisation for men aged 55-64 in 1971. The effects were weaker for women. Moving into rented accommodation was a predictor of both outcomes for women and of death for the younger cohort of men. People who started to live alone in the inter-census period were at reduced risk of dying. These results demonstrate persistence of inequalities in health related outcomes throughout old age, both in those with unfavourable circumstances in mid-life and in those who, in later life, have lost earlier advantages. [ABSTRACT FROM AUTHOR]

To assess the feasibility of conducting a re-survey of men who are resident in the United Kingdom 25 years after enrollment in the Whitehall study of London Civil Servants. A random sample of 401 study survivors resident in three health authority areas was selected for this pilot study. They were mailed a request to complete a self administered questionnaire, and then asked to attend their general practice to have their blood pressure, weight, and height measured and a blood sample collected into a supplied vacutainer, and mailed to a central laboratory. Using a 2 x 2 factorial design, the impact of including additional questions on income and of an informant questionnaire on cognitive function was assessed. Accurate addresses were obtained from the health authorities for 96% of the sample. Questionnaires were received from 73% and blood samples from 61% of the sample. Questions on income had no adverse effect on the response rate, but inclusion of the informant questionnaire did. Between 1970 and 1995 there were substantial changes within men in the mean blood pressure and blood total cholesterol recorded, as reflected by correlation coefficients between 1970 and 1995 values of 0.26, and 0.30 for systolic and diastolic blood pressure and 0.38 for total cholesterol. This pilot study demonstrated the feasibility of conducting a re-survey using postal questionnaires and mailed whole blood samples. The magnitude of change in blood pressure and blood total cholesterol concentrations within individuals was greater than anticipated, suggesting that such remeasurements may be required at different intervals in prospective studies to help interpret risks associations properly. These issues will be considered in a re-survey of the remaining survivors of the Whitehall study. [ABSTRACT FROM AUTHOR]

A COMPREHENSIVE review of the scientific litera ture on adolescent smoking published in English since 1970 shows a remarkable worldwide pattern of development in adolescent smoking. One developed country after another has reported figures showing that girls now have a higher prevalence than boys. No single factor known to be associated with the uptake of smoking in this age range would have had a large enough effect or changed enough to account for this phenomenon. Advertising and the introduction of low-tar cigarettes may have partly contributed to this development, but a new hypothesis is proposed. The fact that girls mature earlier has combined with a steady change in social attitudes, helped by the commercial pressures, so that girls now exhibit smoking behaviour similar to boys one or more years older. Advertising aimed at young women must be discouraged, and anti-smoking education pro grammes in schools should be revised with particu lar reference to their relevance for adolescent girls. [ABSTRACT FROM PUBLISHER]