Developmental and reproductive toxicity hazard characterization of 2-amino-2-methyl-1-propanol (AMP).

2-Amino-2-methyl-1-propanol (AMP™) is a widely used pH stabilizer in personal care products (PCPs); thus, the safety implications of dermal AMP exposure remain of interest. We have previously reported that exposure to AMP in PCPs when used as intended is not anticipated to result in an increased risk of hepatotoxicity (primarily steatosis and altered phospholipid homeostasis). The current study focuses on AMP in PCP's potential for developmental and reproductive toxicity (DART) in humans, based on data from animal studies. Animal studies suggest that exposure to AMP can result in post-implantation loss. However, such effects occur at maternally toxic doses, posing a challenge for determining appropriate hazard classifications in the context of relevant consumer use scenarios. Our assessment concluded that human exposure to AMP in PCPs is not anticipated to result in DART at non-maternally toxic doses. Further, mode of action (MOA) analysis elucidated the potential biological pathways underlying DART effects observed in high-dose animal studies, such that perturbation of uterine choline synthesis was the most well-supported MOA hypothesis. Downstream uterine effects might reflect choline-dependent changes in epigenetic control of pathways important for implantation maintenance and uterine cell energetics. Since AMP-induced post-implantation loss occurs at doses higher than pathology related to liver toxicity, maintaining AMP exposures from exceeding the onset dose for maternal liver effects will also be protective of DART effects. Furthermore, dermal exposure to AMP expected from the use of PCPs is highly unlikely to result in toxicologically significant systemic AMP concentrations; thus, DART is not anticipated.

Development of a framework for risk assessment of dietary carcinogens.

Although there are a number of guidance documents and frameworks for evaluation of carcinogenicity, none of the current methods fully reflects the state of the science. Common limitations include the absence of dose-response assessment and not considering the impact of differing exposure patterns (e.g., intermittent, high peaks vs. lower, continuous exposures). To address these issues, we have developed a framework for risk assessment of dietary carcinogens. This framework includes an enhanced approach for weight of evidence (WOE) evaluation for genetic toxicology data, with a focus on evaluating studies based on the most recent testing guidance to determine whether a chemical is a mutagen. Included alongside our framework is a discussion of resources for evaluating tissue dose and the temporal pattern of internal dose, taking into account the chemical's toxicokinetics. The framework then integrates the mode of action (MOA) and associated dose metric category with the exposure data to identify the appropriate approach(es) to low-dose extrapolation and level of concern associated with the exposure scenario. This framework provides risk managers with additional flexibility in risk management and risk communication options, beyond the binary choice of linear low-dose extrapolation vs. application of uncertainty factors.

Tailoring Writability and Performance of Star Block Copolypeptides Hydrogels through Side-Chain Design.

Shear-recoverable hydrogels based on block copolypeptides with rapid self-recovery hold potential in extrudable and injectable 3D-printing applications. In this work, a series of 3-arm star-shaped block copolypeptides composed of an inner hydrophilic poly(l-glutamate) domain and an outer ß-sheet forming domain is synthesized with varying side chains and block lengths. By changing the ß-sheet forming domains, hydrogels with diverse microstructures and mechanical properties are prepared and structure-function relationships are determined using scattering and rheological techniques. Differences in the properties of these materials are amplified during direct-ink writing with a strong correlation observed between printability and material chemistry. Significantly, it is observed that non-canonical ß-sheet blocks based on phenyl glycine form more stable networks with superior mechanical properties and writability compared to widely used natural amino acid counterparts. The versatile design available through block copolypeptide materials provides a robust platform to access tunable material properties based solely on molecular design. These systems can be exploited in extrusion-based applications such as 3D-printing without the need for additives.

Changes in COVID-19-related mortality across key demographic and clinical subgroups in England from 2020 to 2022: a retrospective cohort study using the OpenSAFELY platform.

BACKGROUND: COVID-19 has been shown to differently affect various demographic and clinical population subgroups. We aimed to describe trends in absolute and relative COVID-19-related mortality risks across clinical and demographic population subgroups during successive SARS-CoV-2 pandemic waves. METHODS: We did a retrospective cohort study in England using the OpenSAFELY platform with the approval of National Health Service England, covering the first five SARS-CoV-2 pandemic waves (wave one [wild-type] from March 23 to May 30, 2020; wave two [alpha (B.1.1.7)] from Sept 7, 2020, to April 24, 2021; wave three [delta (B.1.617.2)] from May 28 to Dec 14, 2021; wave four [omicron (B.1.1.529)] from Dec 15, 2021, to April 29, 2022; and wave five [omicron] from June 24 to Aug 3, 2022). In each wave, we included people aged 18-110 years who were registered with a general practice on the first day of the wave and who had at least 3 months of continuous general practice registration up to this date. We estimated crude and sex-standardised and age-standardised wave-specific COVID-19-related death rates and relative risks of COVID-19-related death in population subgroups. FINDINGS: 18 895 870 adults were included in wave one, 19 014 720 in wave two, 18 932 050 in wave three, 19 097 970 in wave four, and 19 226 475 in wave five. Crude COVID-19-related death rates per 1000 person-years decreased from 4·48 deaths (95% CI 4·41-4·55) in wave one to 2·69 (2·66-2·72) in wave two, 0·64 (0·63-0·66) in wave three, 1·01 (0·99-1·03) in wave four, and 0·67 (0·64-0·71) in wave five. In wave one, the standardised COVID-19-related death rates were highest in people aged 80 years or older, people with chronic kidney disease stage 5 or 4, people receiving dialysis, people with dementia or learning disability, and people who had received a kidney transplant (ranging from 19·85 deaths per 1000 person-years to 44·41 deaths per 1000 person-years, compared with from 0·05 deaths per 1000 person-years to 15·93 deaths per 1000 person-years in other subgroups). In wave two compared with wave one, in a largely unvaccinated population, the decrease in COVID-19-related mortality was evenly distributed across population subgroups. In wave three compared with wave one, larger decreases in COVID-19-related death rates were seen in groups prioritised for primary SARS-CoV-2 vaccination, including people aged 80 years or older and people with neurological disease, learning disability, or severe mental illness (90-91% decrease). Conversely, smaller decreases in COVID-19-related death rates were observed in younger age groups, people who had received organ transplants, and people with chronic kidney disease, haematological malignancies, or immunosuppressive conditions (0-25% decrease). In wave four compared with wave one, the decrease in COVID-19-related death rates was smaller in groups with lower vaccination coverage (including younger age groups) and conditions associated with impaired vaccine response, including people who had received organ transplants and people with immunosuppressive conditions (26-61% decrease). INTERPRETATION: There was a substantial decrease in absolute COVID-19-related death rates over time in the overall population, but demographic and clinical relative risk profiles persisted and worsened for people with lower vaccination coverage or impaired immune response. Our findings provide an evidence base to inform UK public health policy for protecting these vulnerable population subgroups. FUNDING: UK Research and Innovation, Wellcome Trust, UK Medical Research Council, National Institute for Health and Care Research, and Health Data Research UK.

Carcinogenicity of Poorly Soluble Low Toxicity Particles: Commentary on Epidemiology as a Risk Assessment "Reality Check".

Inhaled particles that are poorly soluble or insoluble and of low toxicity ("poorly soluble low toxicity" or "PSLT" particles), can accumulate in the lung and at lung overload levels induce lung cancers in rats. The question of whether PSLT particles increase lung cancer risk in humans is complicated by large differences between rats and humans and the relatively large particle doses administered in animal studies even when compared with heavy human occupational exposures. We review the findings of epidemiological studies on occupational exposure to each of three different PSLT particles (carbon black, talc and taconite). The epidemiological evidence indicates that at even very high occupational exposure levels at which non-malignant respiratory diseases including pneumoconiosis and even talcosis are observed, lung cancer risks appear not to be elevated. Although positive human cancer risks might be predicted based on extrapolation from overload doses in rats to relevant exposures in humans, the epidemiological "reality check" based on the three examples indicates that these PSLT particles are unlikely to increase lung cancer risk in humans even at high occupational levels of exposure. Therefore, we propose that careful evaluation of the epidemiological evidence can serve as a "reality check" for human risk assessment and help balance the risk evaluation process.

Safety of COVID-19 vaccination and acute neurological events: A self-controlled case series in England using the OpenSAFELY platform.

INTRODUCTION: We investigated the potential association of COVID-19 vaccination with three acute neurological events: Guillain-Barré syndrome (GBS), transverse myelitis and Bell's palsy. METHODS: With the approval of NHS England we analysed primary care data from >17 million patients in England linked to emergency care, hospital admission and mortality records in the OpenSAFELY platform. Separately for each vaccine brand, we used a self-controlled case series design to estimate the incidence rate ratio for each outcome in the period following vaccination (4-42 days for GBS, 4-28 days for transverse myelitis and Bell's palsy) compared to a within-person baseline, using conditional Poisson regression. RESULTS: Among 7,783,441 ChAdOx1 vaccinees, there was an increased rate of GBS (N = 517; incidence rate ratio 2·85; 95% CI2·33-3·47) and Bell's palsy (N = 5,350; 1·39; 1·27-1·53) following a first dose of ChAdOx1 vaccine, corresponding to 11.0 additional cases of GBS and 17.9 cases of Bell's palsy per 1 million vaccinees if causal. For GBS this applied to the first, but not the second, dose. There was no clear evidence of an association of ChAdOx1 vaccination with transverse myelitis (N = 199; 1·51; 0·96-2·37). Among 5,729,152 BNT162b2 vaccinees, there was no evidence of any association with GBS (N = 283; 1·09; 0·75-1·57), transverse myelitis (N = 109; 1·62; 0·86-3·03) or Bell's palsy (N = 3,609; 0·89; 0·76-1·03). Among 255,446 mRNA-1273 vaccine recipients there was no evidence of an association with Bell's palsy (N = 78; 0·88, 0·32-2·42). CONCLUSIONS: COVID-19 vaccines save lives, but it is important to understand rare adverse events. We observed a short-term increased rate of Guillain-Barré syndrome and Bell's palsy after first dose of ChAdOx1 vaccine. The absolute risk, assuming a causal effect attributable to vaccination, was low.

Herniation of the bladder through suprapubic catheter tract - An unusual complication.

Long-term complications of suprapubic catheters are not well documented in the literature. The common complications includes infection, stone formation, urine leakage and malignant changes. We report an unusual complication of bladder prolapse in a patient with long-term suprapubic catheterization. Due to the rarity of this complication, its management has not been well studied.

Dose and exposure route analyses inform relationships between liver steatosis and 2-amino-2-methyl-1-propanol: Implications for hazard characterization.

2-Amino-2-methyl-1-propanol (AMP™) is widely used as a neutralizer/pH stabilizer in personal care products (PCPs); however, the potential health implications of dermal AMP exposure remain to be fully elucidated. Consequently, an in-depth analysis was performed to determine if PCPs containing AMP pose an elevated risk in humans under the intended use conditions. Animal studies have shown that at high doses, oral AMP exposure could lead to liver steatosis; thus, this study focused on hepatotoxicity. Our assessment revealed that the derived margin of exposure (MoE) values for AMP-containing PCPs were above 100, indicating that dermal exposure to AMP is unlikely to present an elevated risk of hepatotoxicity. Further, mode of action (MOA) analysis was conducted to elucidate the potential mechanisms underlying the observed hepatotoxicity in animal studies. Our analysis proposed that AMP interferes with the CDP-choline pathway in hepatocytes via the inhibition of one or more enzymes integral to the pathway and/or the replacement of choline in the assembly of the phospholipid unit. Ultimately, these events halt the lipid export via very low-density lipoproteins, which can subsequently develop into fatty liver accompanied by hepatotoxicity and other pathological changes if AMP exposure persists at sufficiently high doses. MOA analysis corroborated that dermal exposure to AMP expected from use of PCPs is highly unlikely to result in toxicologically significant systemic concentrations of AMP and thus hepatotoxicity. We concluded that dermal exposure to AMP in PCPs is not anticipated to result in an increased risk of hepatotoxicity.

Epstein-Barr-virus-positive large B-cell lymphoma associated with breast implants: an analysis of eight patients suggesting a possible pathogenetic relationship.

Breast implant anaplastic large cell lymphoma (ALCL) is a T-cell neoplasm arising around textured breast implants that was recognized recently as a distinct entity by the World Health Organization. Rarely, other types of lymphoma have been reported in patients with breast implants, raising the possibility of a pathogenetic relationship between breast implants and other types of lymphoma. We report eight cases of Epstein-Barr virus (EBV)-positive large B-cell lymphoma associated with breast implants. One of these cases was invasive, and the other seven neoplasms were noninvasive and showed morphologic overlap with breast implant ALCL. All eight cases expressed B-cell markers, had a non-germinal center B-cell immunophenotype, and were EBV+ with a latency type III pattern of infection. We compared the noninvasive EBV+ large B-cell lymphoma cases with a cohort of breast implant ALCL cases matched for clinical and pathologic stage. The EBV+ large B-cell lymphoma cases more frequently showed a thicker capsule, and more often were associated with calcification and prominent lymphoid aggregates outside of the capsule. The EBV+ B-cell lymphoma cells were more often arranged within necrotic fibrinoid material in a layered pattern. We believe that this case series highlights many morphologic similarities between EBV+ large B-cell lymphoma and breast implant ALCL. The data presented suggest a pathogenetic role for breast implants (as well as EBV) in the pathogenesis of EBV+ large B-cell lymphoma. We also provide some histologic findings useful for distinguishing EBV+ large B-cell lymphoma from breast implant ALCL in this clinical setting.

Current process and outcomes of the surgical management of LUTS due to benign prostatic enlargement: how consistent are we? - results from the multi-institutional audit of surgical management of BPE (AuSuM BPE) in the United Kingdom.

OBJECTIVE: In view of changing landscape of surgical treatment for LUTS secondary to BPE, this audit was undertaken to assess key aspects of the processes and outcomes of the current interventional treatments for BPE, across different units in the UK. MATERIALS AND METHOD: A multi-institutional snapshot audit was conducted for patients undergoing interventions for LUTS/BPE over 8-week period. Using Delphi process two-part proforma was designed to capture data. RESULTS: 529 patients were included across 20 NHS trusts in England and Wales. Median age was 73 years. Indications for surgery were acute retention (47%) and LUTS (45%). 80% of patients had prior medical therapy. TURP formed the commonest procedure. 27% patients had <23 hour hospital stay. Immediate (21%) and delayed (18%) complications were Clavien-Dindo <2 category. High proportion of patients reported residual symptoms. Type and indication of surgery were significant predictor of complications, length of stay and failure of TWOC outcomes, on multivariate analyses. There were variations in departmental processes, 50% centres used PROMs. CONCLUSION: Monopolar TURP still remains the commonest intervention for BPE. Most departments are adopting newer technologies. The audit identified opportunities for development of consistent, effective and patient centric practices as well as need for large-scale focused studies.

A Systematic Review of UK Educational and Training Materials Aimed at Health and Social Care Staff about Providing Appropriate Services for LGBT+ People.

BACKGROUND: There is greater dissatisfaction with health services by LGBT people compared to heterosexual and cisgender people and some of this is from lack of equality and diversity training for health professionals. Core training standards in sexual orientation for health professionals have been available since 2006. The purpose of this project is to systematically review educational materials for health and social care professionals in lesbian, gay, bisexual, and transgender (LGBT) issues. METHODS: A protocol was developed and searches conducted in six databases. SELECTION CRITERIA: any studies reporting delivery or evaluation of UK education of health and/or social care professionals in LGBT issues, with no language or setting restrictions. Inclusions and data extraction were conducted in duplicate. Narrative synthesis of educational evaluations was used. Educational materials were assessed using thematic synthesis. RESULTS: From the searches, 165 full papers were evaluated and 19 studies were included in the narrative synthesis. Three were successful action-research projects in cancer services and in residential care. Sixteen sets of educational/training materials have been available since 2010. These varied in length, scope, target audience, and extent of development as classroom-ready materials. CONCLUSIONS: Despite the availability of appropriate training programmes for post-qualifying staff, recommendations to undertake training, best practice examples, and statements of good intent, LGBT people continue to report that they are experiencing discrimination or direct prejudice from health and/or social care services. Better training strategies using behaviour change techniques are needed.

Cancer control in small island nations: from local challenges to global action.

Cancer is a leading cause of death in small island nations and is forecast to increase substantially over the coming years. Governments, regional agencies, and health services of these nations face daunting challenges, including small and fragile economies, unequal distribution of resources, weak or fragmented health services, small population sizes that make sustainable workforce and service development problematic, and the unavailability of specialised cancer services to large parts of the population. Action is required to prevent large human and economic costs relating to cancer. This final Series paper highlights the challenges and opportunities for small island nations, and identifies ways in which the international community can support efforts to improve cancer control in these settings. Our recommendations focus on funding and investment opportunities to strengthen cancer-related health systems to improve sharing of technical assistance for research, surveillance, workforce, and service development, and to support small island nations with policy changes to reduce the consumption of commodities (eg, tobacco and unhealthy food products) that increase cancer risk.

Nicorandil-induced penile ulceration: a case report.

BACKGROUND: Penile ulceration in older patients is commonly neoplastic or infective. However, there are rarer causes of these ulcerations that we have to exclude. We present a rare complication of penile ulceration secondary to nicorandil, a nicotinamide ester. CASE PRESENTATION: An 86-year-old white British man was referred with a bloody discharge from under his phimotic foreskin and a lump on the shaft of his penis for the past year. He had angina which has been controlled with nicorandil for the past 5 years. A surgical biopsy of the ulcer showed inflammation with no evidence of malignancy. His penile ulceration spontaneously resolved when he stopped his nicorandil treatment. CONCLUSIONS: Nicorandil-induced ulceration is a rare complication; however, it should not be missed in a clinical setting. If there is any doubt about the cause of penile ulceration, then referral to dermatology or urology for consideration of biopsy is essential.

Regulation of copper transport crossing brain barrier systems by Cu-ATPases: effect of manganese exposure.

Regulation of cellular copper (Cu) homeostasis involves Cu-transporting ATPases (Cu-ATPases), i.e., ATP7A and ATP7B. The question as to how these Cu-ATPases in brain barrier systems transport Cu, i.e., toward brain parenchyma, cerebrospinal fluid (CSF), or blood, remained unanswered. This study was designed to characterize roles of Cu-ATPases in regulating Cu transport at the blood-brain barrier (BBB) and blood-CSF barrier (BCB) and to investigate how exposure to toxic manganese (Mn) altered the function of Cu-ATPases, thereby contributing to the etiology of Mn-induced parkinsonian disorder. Studies by quantitative real-time RT-PCR (qPCR), Western blot, and immunocytochemistry revealed that both Cu-ATPases expressed abundantly in BBB and BCB. Transport kinetic studies by in situ brain infusion and ventriculo-cisternal (VC) perfusion in Sprague Dawley rat suggested that the BBB was a major site for Cu entry into brain, whereas the BCB was a predominant route for Cu efflux from the CSF to blood. Confocal evidence showed that the presence of excess Cu or Mn in the choroid plexus cells led to ATP7A relocating toward the apical microvilli facing the CSF, but ATP7B toward the basolateral membrane facing blood. Mn exposure inhibited the production of both Cu-ATPases. Collectively, these data suggest that Cu is transported by the BBB from the blood to brain, which is mediated by ATP7A in brain capillary. By diffusion, Cu ions move from the interstitial fluid into the CSF, where they are taken up by the BCB. Within the choroidal epithelial cells, Cu ions are transported by ATP7B back to the blood. Mn exposure alters these processes, leading to Cu dyshomeostasis-associated neuronal injury.

Age-related degenerative functional, radiographic, and histological changes of the shoulder in nonhuman primates.

BACKGROUND: Nonhuman primates have similar shoulder anatomy and physiology compared to humans, and may represent a previously underutilized model for shoulder research. This study sought to identify naturally occurring bony and muscular degeneration in the shoulder of nonhuman primates and to assess relationships between structural and functional aspects of the shoulder and measures of physical function of the animals. We hypothesized that age-related degenerative changes in the shoulders of nonhuman primates would resemble those observed in aging humans. METHODS: Middle-aged (n = 5; ages 9.4-11.8 years) and elderly (n = 6; ages 19.8-26.4 years) female vervet monkeys were studied for changes in mobility and shoulder function, and radiographic and histologic signs of age-related degeneration. RESULTS: Four out of 6 (4/6) elderly animals had degenerative changes of the glenoid compared to 0/5 of the middle-aged animals (P = .005). Elderly animals had glenoid retroversion, decreased joint space, walked slower, and spent less time climbing and hanging than middle-aged vervets (P < .05). Physical mobility and shoulder function correlated with glenoid version angle (P < .05). Supraspinatus muscles of elderly animals were less dense (P = .001), had decreased fiber cross-sectional area (P < .001), but similar amounts of nuclear material (P = .085). Degenerative rotator cuff tears were not observed in any of the eleven animals. DISCUSSION AND CONCLUSION: The vervet monkey naturally undergoes age-related functional, radiographic and histological changes of the shoulder, and may qualify as an animal model for selected translational research of shoulder osteoarthritis.

Soft tissue attachment to titanium implants coated with growth factors.

BACKGROUND: Enhancing the connective tissue seal around dental implants may be an important factor in implant survival. PURPOSE: The objective of the study was to investigate the effect of implant surface modification with either platelet-derived growth factor (PDGF) or enamel matrix derivative (EMD) on connective tissue attachment to titanium implants. MATERIALS AND METHODS: Eighteen implants (Branemark® Mk III Groovy NP (3.3 mmØ × 10 mm, Nobel Biocare) were implanted subcutaneously into 12 rats. Six implants each were coated with either PDGF or EMD immediately prior to implantation and six implants were left uncoated. Implants were retrieved at 4 and 8 weeks and assessed histologically to compare the soft tissue adaptation to the implant surfaces. RESULTS: Ingrowth by soft connective tissue into the threads of all implants was noted at 4 and 8 weeks. Coating with growth factors did not alter the orientation of fibroblasts and collagen fibers. The depth of connective tissue penetration into the implant grooves was significantly greater for the implants coated with PDGF at 4 weeks. The thickness of the connective tissue in growth was significantly less for the implants coated with PDGF at 8 weeks. CONCLUSION: Coating of the implant surface with rhPDGF-BB or EMD can increase the speed and quantity of soft tissue healing around the implant surface.

Spatial classification of youth physical activity patterns.

BACKGROUND: Physical activity is an essential element in reducing the prevalence of obesity, but much is unknown about the intensity and location of physical activity among youth-this is important because adolescent health behaviors are predictive of behaviors in adults. PURPOSE: This study aims to identify the locations where youth moderate-to-vigorous physical activity (MVPA) occurs, and to examine how MVPA varies according to urbanicity (urban, suburban, rural). METHODS: Participants included adolescent students (N=380, aged 12-16 years) from Halifax, Nova Scotia. Locations of MVPA were measured using accelerometers and GPS data loggers for up to 7 days. Specialized software was developed to integrate and process the data. Frequencies of MVPA by location were determined, and differences in MVPA were assessed for association with urbanicity. RESULTS: Active commuting accounted for the largest proportion of time in MVPA among urban and suburban students. Rural students achieved most MVPA at school. Other residential locations, shopping centers, and green spaces accounted for a majority of the remaining MVPA. Minutes in MVPA varied significantly overall (196.6 ± 163.8, 84.9 ± 103.2, 81.7 ± 98.2); at school (45.7 ± 45.2, 18.6 ± 28.0, 29.8 ± 39.7); while commuting (110.3 ± 107.1, 31.5 ± 55.2, 19.5 ± 39.7); and at other activity locations (19.7 ± 27.1, 14.8 ± 26.8, 12.0 ± 22.1) and by urbanicity. CONCLUSIONS: Findings reveal that the journeys between locations are as important as home and school settings in contributing to greater MVPA in adolescent youth. The relative importance of context as a contributor to MVPA varies with urbanicity. Combining actimetry and GPS data provides a precise link between physical activity measurements and contexts of the built environment.

Redox-modulatory vitamins and minerals that prospectively predict mortality in older British people: the National Diet and Nutrition Survey of people aged 65 years and over.

The predictive power, for total, vascular, cancer and respiratory mortality, of selected redox-modulatory (vitamin and mineral nutrient) indices measured at baseline, was studied in the British National Diet and Nutrition Survey (community-living subset) of people aged 65 years and over. Mortality status and its primary and underlying causes were recorded for 1054 (mean age 76·6 (sd 7·4) years and 49·0 % female) participants, from the baseline survey in 1994­5 until September 2008. During this interval, 74 % of the male and 62 % of the female participants died. Total mortality was significantly predicted by baseline plasma concentrations (per sd) of vitamin C (hazard ratio (HR) 0·81; 95 % CI 0·74, 0·88), α-carotene (HR 0·90; 95 % CI 0·81, 0·99), Se (HR 0·76; 95 % CI 0·69, 0·84), Zn (HR 0·79; 95 % CI 0·72, 0·87), Cu (HR 1·27; 95 % CI 1·14, 1·42) and Fe (HR 0·81; 95 % CI 0·74, 0·89). Total mortality was also significantly predicted by baseline dietary intakes (per sd) of food energy (HR 0·86; 95 % CI 0·79, 0·94), vitamin C (HR 0·88; 95 % CI 0·80, 0·94), carotenoids (HR 0·89; 95 % CI 0·83, 0·96), Zn (HR 0·89; 95 % CI 0·82, 0·96) and Cu (HR 0·91; 95 % CI 0·84, 1·00). Prediction patterns and significance for primary vascular, cancer and respiratory mortality differed in certain respects, but not fundamentally. Model adjustment for known disease or mortality risk predictors resulted in loss of significance for some of the indices; however, plasma Se and Zn, and food energy remained significant predictors. We conclude that total and primary vascular, cancer and respiratory mortality in older British people of both sexes is predicted by several biochemical indices of redox-modulatory nutrients, some of which may reflect the respondents' acute-phase status at baseline, whereas others may reflect the healthiness of their lifestyle.

Depression, physical function, and risk of mortality: National Diet and Nutrition Survey in adults older than 65 years.

OBJECTIVE: the authors used an objective assessment of physical function and a range of sociodemographic, dietary, and health behaviors to explore the possible factors that could explain the association between depression and mortality in community-dwelling elderly participants aged 65 years and older. DESIGN: prospective follow-up of the National Diet and Nutrition Survey in older adults. SETTING: community sample. PARTICIPANTS: a total of 1,007 participants (522 men, 485 women; mean age: 76.4 ± 7.3 years). MEASUREMENTS: : Depression was assessed from the 15 item Geriatric Depression Scale (GDS) and physical function using hand grip strength. Participants were followed up for death over an average of 9.2 years. RESULTS: : At baseline, 20.9% of participants demonstrated depression (GDS-15 score ≥ 5). Depressed participants were at a higher relative risk of all cause mortality during follow-up (age- and sex-adjusted hazard ratio = 1.24, 95% confidence interval: 1.04-1.49). Other risk factors for depression also related to mortality included smoking, physical inactivity, and low grip strength. These factors collectively explained an estimated 54% of the association between depression and mortality. Low-grade inflammation and low plasma vitamin C were also independently associated with depression and mortality but did not explain any of the association between depression and mortality. CONCLUSION: late-life depression is associated with a higher risk of mortality. Physical inactivity and physical dysfunction might partly mediate this association, although further longitudinal studies are required to fully elucidate these mechanisms.