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Background: Previous researched has demonstrated potent health and survival advantages across three-generations in longevity-enriched families. However, the survival advantage associated with familial longevity may manifest earlier in life than previously thought. Methods: We conducted a matched cohort study comparing early health trajectories in third-generation grandchildren (n = 5,637) and fourth-generation great-grandchildren (n = 14,908) of longevity-enriched sibships to demographically matched births (n = 41,090) in Denmark between 1973 and 2018. Results: Lower risk was observed across a range of adverse early life outcomes in the grandchildren, including infant mortality (Hazard Ratio (HR) = 0.53, 95% CI [0.36, 0.77]), preterm birth (Odds Ratio (OR) = 0.82, [0.72, 0.93]), small for gestational age (OR = 0.83, [0.76, 0.90]) and neonatal respiratory disorders (OR = 0.77, [0.67, 0.88]). Relative advantages in parental education and maternal smoking were observed in both generations to a similar degree. However, a much smaller reduction in infant mortality was observed in the great-grandchildren (HR = 0.90, [0.70, 1.17]) and benefits across other outcomes were also less consistent, despite persisting socioeconomic and behavioural advantages. Lastly, maternal, and paternal lines of transmission were equipotent in the transmission of infant survival advantages. Conclusions: Descendants of longevity-enriched sibships exhibit a broad health advantage manifesting as early the perinatal period. However, this effect is strongly diluted over successive generations. Our findings suggest that exceptional health and survival may have early developmental components and implicate heritable genetic and or epigenetic factors in their specific transmission.
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Diatoms are globally abundant microalgae that form extensive blooms in aquatic ecosystems. Certain bacteria behave antagonistically towards diatoms, killing or inhibiting their growth. Despite their crucial implications to diatom blooms and population health, knowledge of diatom antagonists in the environment is fundamentally lacking. We report systematic characterisation of the diversity and seasonal dynamics of bacterial antagonists of diatoms via plaque assay sampling in the Western English Channel (WEC), where diatoms frequently bloom. Unexpectedly, peaks in detection did not occur during characteristic spring diatom blooms, but coincided with a winter bloom of Coscinodiscus, suggesting that these bacteria likely influence distinct diatom host populations. We isolated multiple bacterial antagonists, spanning 4 classes and 10 bacterial orders. Notably, a diatom attaching Roseobacter Ponticoccus alexandrii was isolated multiple times, indicative of a persistent environmental presence. Moreover, many isolates had no prior reports of antagonistic activity towards diatoms. We verified diatom growth inhibitory effects of eight isolates. In all cases tested, these effects were activated by pre-exposure to diatom organic matter. Discovery of widespread 'cryptic' antagonistic activity indicates that bacterial pathogenicity towards diatoms is more prevalent than previously recognised. Finally, examination of the global biogeography of WEC antagonists revealed co-occurrence patterns with diatom host populations in marine waters globally.
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Diatomeas , Microalgas , Ecosistema , Estaciones del Año , BacteriasRESUMEN
Photosynthesis by marine diatoms contributes significantly to the global carbon cycle. Due to the low concentration of CO2 in seawater, many diatoms use extracellular carbonic anhydrase (eCA) to enhance the supply of CO2 to the cell surface. While much research has investigated how the requirement for eCA is influenced by changes in CO2 availability, little is known about how eCA contributes to CO2 supply following changes in the demand for carbon. We therefore examined how changes in photosynthetic rate influence the requirement for eCA in three centric diatoms. Modeling of cell surface carbonate chemistry indicated that diffusive CO2 supply to the cell surface was greatly reduced in large diatoms at higher photosynthetic rates. Laboratory experiments demonstrated a trend of an increasing requirement for eCA with increasing photosynthetic rate that was most pronounced in the larger species, supporting the findings of the cellular modeling. Microelectrode measurements of cell surface pH and O2 demonstrated that individual cells exhibited an increased contribution of eCA to photosynthesis at higher irradiances. Our data demonstrate that changes in carbon demand strongly influence the requirement for eCA in diatoms. Cell size and photosynthetic rate will therefore be key determinants of the mode of dissolved inorganic carbon uptake.
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Anhidrasas Carbónicas , Diatomeas , Diatomeas/metabolismo , Anhidrasas Carbónicas/metabolismo , Carbono/metabolismo , Dióxido de Carbono/metabolismo , Carbonatos/metabolismo , FotosíntesisRESUMEN
BACKGROUND: Previous research has suggested that individuals with Type 2 diabetes and initiated on metformin monotherapy present with a survival advantage compared with the general population without diabetes. This finding has generated considerable interest in the prophylactic use of metformin against age-related morbidity. METHODS: Utilizing Danish National Health Registers, we assessed differences in survival associated with metformin monotherapy for Type 2 diabetes compared with no diagnosis of diabetes in both singleton and discordant twin populations between 1996 and 2012. Data were analysed in both nested case-control and matched cohort study designs, with incidence rate ratios (IRRs) and hazard ratios estimated using conditional logistic regression and Cox proportional hazards regression, respectively. RESULTS: In case-control pairs matched on birth year and sex or co-twin (sex, birth year and familial factors), incident Type 2 diabetes with treatment by metformin monotherapy initiation compared with no diagnosis of diabetes was associated with increased mortality in both singletons (IRR = 1.52, 95% CI: 1.37, 1.68) and discordant twin pairs (IRR = 1.90, 95% CI: 1.35, 2.67). After adjusting for co-morbidities and social indicators, these associations were attenuated to 1.32 (95% CI: 1.16, 1.50) and 1.64 (95% CI: 1.10, 2.46), respectively. Increased mortality was observed across all levels of cumulative use and invariant to a range of study designs and sensitivity analyses. CONCLUSIONS: Treatment initiation by metformin monotherapy in Type 2 diabetes was not associated with survival equal or superior to that of the general population without diabetes. Our contrasting findings compared with previous research are unlikely to be the result of differences in epidemiological or methodological parameters.
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Diabetes Mellitus Tipo 2 , Metformina , Humanos , Metformina/uso terapéutico , Hipoglucemiantes/uso terapéutico , Estudios de Cohortes , Estudios Retrospectivos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiologíaRESUMEN
BACKGROUND: Population-based organized screening programmes for colorectal cancer (CRC) are underway worldwide, with many based on the faecal immunochemical test (FIT). No clinical trials assessing FIT compared with no screening are planned, and few studies have assessed the population impact of such programmes. METHODS: Before 2010, 11 out of 50 Spanish provinces initiated population-based organized screening programmes with FIT for an average-risk population aged 50-69 years. We used a quasi-experimental design across Spanish provinces between 1999 and 2016 to evaluate their impact on population age-standardized mortality and incidence rates due to CRC. Difference-in-differences and synthetic control analyses were performed to test for validation of statistical assumptions and to assess the dynamics of screening-associated changes in outcomes over time. RESULTS: No differences in outcome trends between exposed (n = 11) and control (n = 36) provinces were observed for up to 7 years preceding the implementation of screening. Relative to controls, exposed provinces experienced a mean increase in age-standardized incidence of 10.08% [95% confidence interval (CI) (5.09, 15.07)] 2 years after implementation, followed by a reduction in age-standardized mortality rates due to CRC of 8.82% [95% CI (3.77, 13.86)] after 7 years. Results were similar for both women and men. No associated changes were observed in adjacent age bands not targeted by screening, nor for 10 other major causes of death in the exposed provinces. CONCLUSIONS: FIT-based organized screening in Spain was associated with reductions in population colorectal cancer mortality. Further research is warranted in order to assess the replicability and external validity of our findings, and on gender-specific use of FIT in organized screening.
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Neoplasias Colorrectales , Detección Precoz del Cáncer , Niño , Neoplasias Colorrectales/diagnóstico , Femenino , Humanos , Masculino , Tamizaje Masivo , Sangre Oculta , España/epidemiologíaRESUMEN
BACKGROUND: Infections with multidrug resistant (MDR) bacteria in hospital settings have substantial implications in terms of clinical and economic outcomes. However, due to clinical and methodological heterogeneity, estimates about the attributable economic and clinical effects of healthcare-associated infections (HAI) due to MDR microorganisms (MDR HAI) remain unclear. The objective was to review and synthesize the evidence on the impact of MDR HAI in adults on hospital costs, length of stay, and mortality at discharge. METHODS AND FINDINGS: Literature searches were conducted in PubMed/MEDLINE, and Google Scholar databases to select studies that evaluated the impact of MDR HAI on economic and clinical outcomes. Eligible studies were conducted in adults, in order to ensure homogeneity of populations, used propensity score matched cohorts or included explicit confounding control, and had confirmed antibiotic susceptibility testing. Risk of bias was evaluated, and effects were measured with ratios of means (ROM) for cost and length of stay, and risk ratios (RR) for mortality. A systematic search was performed on 14th March 2019, re-run on the 10th of June 2019 and extended the 3rd of September 2019. Small effect sizes were assessed by examination of funnel plots. Sixteen articles (6,122 patients with MDR HAI and 8,326 patients with non-MDR HAI) were included in the systematic review of which 12 articles assessed cost, 19 articles length of stay, and 14 mortality. Compared to susceptible infections, MDR HAI were associated with increased cost (ROM 1.33, 95%CI [1.15; 1.54]), prolonged length of stay (ROM 1.27, 95%CI [1.18; 1.37]), and excess in-hospital mortality (RR 1.61, 95%CI [1.36; 1.90]) in the random effects models. Risk of publication bias was only found to be significant for mortality, and overall study quality good. CONCLUSIONS: MDR HAI appears to be strongly associated with increases in direct cost, prolonged length of stay and increased mortality. However, further comprehensive studies in this setting are warranted. TRIAL REGISTRATION: PROSPERO (CRD42019126288).
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Infección Hospitalaria/economía , Farmacorresistencia Bacteriana Múltiple , Adulto , Infección Hospitalaria/microbiología , Infección Hospitalaria/mortalidad , Costos de Hospital , Mortalidad Hospitalaria , Humanos , Tiempo de Internación , Resultado del TratamientoRESUMEN
A 21-year time series of phytoplankton community structure was analysed in relation to Phaeocystis spp. to elucidate its contribution to the annual carbon budget at station L4 in the western English Channel (WEC). Between 1993-2014 Phaeocystis spp. contributed â¼4.6% of the annual phytoplankton carbon and during the March - May spring bloom, the mean Phaeocystis spp. biomass constituted 17% with a maximal contribution of 47% in 2001. Upper maximal weekly values above the time series mean ranged from 63 to 82% of the total phytoplankton carbon (â¼42-137mg carbon (C)m-3) with significant inter-annual variability in Phaeocystis spp. Maximal biomass usually occurred by the end of April, although in some cases as early as mid-April (2007) and as late as late May (2013). The effects of elevated pCO2 on the Phaeocystis spp. spring bloom were investigated during a fifteen-day semi-continuous microcosm experiment. The phytoplankton community biomass was estimated at â¼160mgCm-3 and was dominated by nanophytoplankton (40%, excluding Phaeocystis spp.), Phaeocystis spp. (30%) and cryptophytes (12%). The smaller fraction of the community biomass comprised picophytoplankton (9%), coccolithophores (3%), Synechococcus (3%), dinoflagellates (1.5%), ciliates (1%) and diatoms (0.5%). Over the experimental period, total biomass increased significantly by 90% to â¼305mgCm-3 in the high CO2 treatment while the ambient pCO2 control showed no net gains. Phaeocystis spp. exhibited the greatest response to the high CO2 treatment, increasing by 330%, from â¼50mgCm-3 to over 200mgCm-3 and contributing â¼70% of the total biomass. Taken together, the results of our microcosm experiment and analysis of the time series suggest that a future high CO2 scenario may favour dominance of Phaeocystis spp. during the spring bloom. This has significant implications for the formation of hypoxic zones and the alteration of food web structure including inhibitory feeding effects and lowered fecundity in many copepod species.
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Biomasa , Dióxido de Carbono/farmacología , Eutrofización/efectos de los fármacos , Fitoplancton/crecimiento & desarrollo , Estaciones del Año , Carbonatos/metabolismo , Clorofila A/metabolismo , Inglaterra , Geografía , Modelos Lineales , Fitoplancton/efectos de los fármacos , Especificidad de la Especie , Factores de TiempoRESUMEN
BACKGROUND AND OBJECTIVES: Ultrasound is a common and necessary part of acute care medicine, but may present an infection risk to patients secondary to transfer of infectious agents between patients. Our primary objective was to detect blood contamination on ultrasound equipment in emergency departments (EDs) and intensive care units. Secondary objectives included detection of microbial contamination and determination of factors associated with contamination. DESIGN AND SETTING: We tested ultrasound equipment used in five EDs and five ICUs for blood and microbial contamination, and collated and analysed contamination data using tables and multiple logistic regression. MAIN OUTCOME MEASURES AND RESULTS: We performed 109 tests for blood and 131 tests for microbial contamination, with 61% of samples testing positive for blood contamination (95% CI, 52%-71%) and 48% testing positive for microbiological contamination (95% CI, 40%-57%). Transducer leads and transducers had high blood contamination (88% and 57%, respectively) and microbiological contamination (62% and 46%, respectively). Equipment from ICUs was less likely to test positive (odds ratio, 0.55; 95% CI, 0.37-0.79). Only 51% of blood-contaminated samples were visibly stained, and visible staining was not associated with microbiological contamination (57%; P=1). CONCLUSION: Our results show significant contamination of ultrasound equipment, and that visual inspection of equipment is neither sufficient nor reliable in excluding contamination. Ultrasound equipment is a possible factor in the transmission of infectious diseases in EDs and ICUs. Guidelines must be formulated, disseminated and rapidly adopted to ensure the safety of the most acutely ill patients exposed to ultrasound procedures in acute care settings.