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Proxy reconstructions suggest that mid-Holocene East African temperatures were warmer than today between 8 and 5 ka BP, but climate models cannot replicate this warming. Precessional forcing caused a shift of maximum insolation from boreal spring to fall in the mid-Holocene, which may have favored intense warming at the start of the warm season. Here, we use three Porites corals from Kenya that represent time windows from 6.55 to 5.87 ka BP to reconstruct past sea surface temperature (SST) seasonality from coral Sr/Ca ratios in the western Indian Ocean during the mid-Holocene. Although the Indian monsoon was reportedly stronger in the mid-Holocene, which should have amplified the seasonal cycle of SST in the western Indian Ocean, the corals suggest reduced seasonality (mean 3.2 °C) compared to the modern record (mean 4.3 °C). Warming in austral spring is followed by a prolonged period of warm SSTs, suggesting that an upper limit of tropical SSTs under mid-Holocene conditions was reached at the start of the warm season, and SSTs then remained stable. Similar changes are seen at the Seychelles. Bootstrap estimates suggest a reduction in SST seasonality of 1.3 ± 0.22 °C at Kenya and 1.7 ± 0.32 °C at the Seychelles. SST seasonality at Kenya corresponds to present-day SST seasonality at 55° E-60° E, while SST seasonality at the Seychelles corresponds to present day SST seasonality at ~ 65° E. This implies a significant westward expansion of the Indian Ocean warm pool. Furthermore, the coral data suggests that SST seasonality deviates from seasonal changes in orbital insolation due to ocean-atmosphere interactions.
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Antozoários , Animais , Oceano Índico , Água do Mar , Quênia , TemperaturaRESUMO
INTRODUCTION: Peripheral artery disease (PAD) is commonly observed in patients undergoing hemodialysis. PAD impairs the vasculature and leads to pathophysiologic changes in the skeletal muscles, causing physical function impairment and physical inactivity in general. However, it is unclear whether PAD adversely affects physical function and physical activity in patients on hemodialysis. METHODS: We performed a cross-sectional study with a retrospective review of the data to determine whether PAD is associated with impaired physical function and physical activity in patients undergoing hemodialysis. The study population comprised 310 patients and 88 healthy subjects. PAD was diagnosed based on an ankle-brachial index of <1.00 in patients on hemodialysis. Measurements of physical function included maximum walking speed, muscle strength in the lower extremities, and balance while standing. FINDINGS: Of the 310 patients, 84 (27.1%) had PAD. When patients undergoing hemodialysis were divided into those without PAD and those with PAD, both groups had poorer physical function and physical activity than the healthy control subjects. After adjustments for potential confounders, it was found that patients on hemodialysis with PAD had slower walking speed, poorer standing balance, and less physical activity than those without PAD. However, there was no significant difference in lower extremity muscle strength between the two groups. DISCUSSION: PAD diagnosed based on an ankle-brachial index of <1.00 was independently associated with impaired physical function and reduced physical activity in patients undergoing hemodialysis.
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Doença Arterial Periférica , Caminhada , Humanos , Estudos Transversais , Diálise Renal/efeitos adversos , Doença Arterial Periférica/etiologia , Doença Arterial Periférica/diagnóstico , Exercício FísicoRESUMO
The Mekong River Delta (MRD) is an essential agricultural area for the worldwide rice supply. Floods and droughts triggered by El Niño southern oscillation (ENSO) have been threatening sustenance in the MRD. Sustainable food supplies require understanding the response of the MRD hydrology to the changing ENSO behaviour in recent decades. Here, we reconstructed the annual rainfall maxima in the MRD using the oceanic paleoclimate proxy from coral skeletons and compared them with ENSO indexes. Annual minima of coral-based seawater oxygen isotope (δ18Osw) correlated with annual rainfall maxima, which allowed to extend rainfall data from 1924 to the recent. The annual rainfall maxima based on δ18Osw negatively correlated with the central Pacific El Niño index. This suggested that La Niña and central Pacific El Niño events lead to heavy and light rainy seasons. The heavy rainy season had more serious impacts in recent decades, which likely increases the flood risk. In contrast, the frequency and rainfall amount of the light rainy season has not changed significantly, although a catastrophic drought has hit the MRD. Our finding concludes that the impact of the ENSO event on MRD hydrology is inconsistent in the past century.
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El Niño Oscilação Sul , HidrologiaRESUMO
The variability of the northern westerlies has been considered as one of the key elements for modern and past climate evolution. Their multiscale behavior and underlying control mechanisms, however, are incompletely understood, owing to the complex dynamics of Atlantic sea-level pressures. Here, we present a multi-annually resolved record of the westerly drift over the past 6,500 years from northern Italy. In combination with more than 20 other westerly-sensitive records, our results depict the non-stationary westerly-affected regions over mainland Europe on multi-decadal to multi-centennial time scales, showing that the direction of the westerlies has changed with respect to the migrations of the North Atlantic centers of action since the middle Holocene. Our findings suggest the crucial role of the migrations of the North Atlantic dipole in modulating the westerly-affected domain over Europe, possibly modulated by Atlantic Ocean variability.
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Clima , Vento , Europa (Continente) , Oceano Atlântico , ItáliaRESUMO
Extreme positive Indian Ocean Dipole (pIOD) events are amplified by non-linear ocean-atmosphere interactions and are characterized by pronounced cooling in the eastern equatorial Indian Ocean. These non-linear feedbacks are not adequately represented in historical products of sea surface temperatures that underestimate the magnitude of extreme pIOD events. Here, we present a sea surface temperature (SST) reconstruction based on monthly coral Sr/Ca ratios measured in two coral cores from Enggano Island (Indonesia), that lies in the eastern pole of the IOD. The coral SST reconstruction extends from 1930 to 2008 and captures the magnitude of cooling during extreme pIOD events as shown in recent satellite and reanalysis data of SST that include ocean dynamics. The corals indicate that the 1961 pIOD event was at least as severe as the 1997 event, while the 1963 pIOD was more comparable to the 2006 event. The magnitude 1967 pIOD is difficult to assess at present due to poor replication between coral cores, and may be comparable to either 1997 or 2006. Cooling during the 1972 pIOD was short-lived and followed by pronounced warming, as seen in the moderate pIOD event of 1982. A combination of coral SST reconstructions and an extension of new reanalysis products of SST to historical time scales could help to better assess the severity and impact of past pIOD events such as the ones seen in the 1960s.
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Antozoários , Animais , Atmosfera , Temperatura Baixa , Recifes de Corais , Oceano Índico , TemperaturaRESUMO
OBJECTIVE: Protein-energy wasting is prevalent among patients undergoing dialysis. Hence, identifying an optimal index is necessary for the comprehensive measurement of nutritional status. This study evaluated and compared the prognostic significance of the modified creatinine index (mCI) and geriatric nutritional risk index (GNRI), with the principal aim to identify markers that are more closely associated with clinical events in patients undergoing hemodialysis. METHODS: We performed a retrospective cohort study of 472 patients undergoing maintenance hemodialysis (mean age, 66.4 years; 62.9% males). We evaluated the mCI, GNRI, and their respective rates of change over a 1-year period. The outcome analysis included all-cause death, number and duration of all-cause hospitalizations, and number and duration of hospitalizations due to cardiovascular disease. In addition, we analyzed the associations of the mCI, GNRI, and their trajectories with clinical outcomes using Cox proportional hazard regression and negative binomial regression. RESULTS: Over a median 3.6-year follow-up, both the lower mCI (hazard ratio 3.00; 95% confidence interval 2.19, 4.09) and lower GNRI (hazard ratio 1.76; 95% confidence interval 1.45, 2.13) per 1 standard deviation decrease were associated with a higher risk of all-cause death. However, a lower mCI was consistently associated with a higher risk of hospitalization, whereas the GNRI was poorly associated with the risk of hospitalization after adjusting for covariates. Furthermore, although a decline in the mCI over time was associated with a higher risk of each adverse event, a significant association between the change in GNRI and clinical events was not detected. CONCLUSION: The mCI at one timepoint and its trajectory had consistently stronger associations with clinical events than the GNRI in patients undergoing hemodialysis. This study further emphasizes the importance of risk screening using a marker of nutritional status in patients undergoing hemodialysis.
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Avaliação Nutricional , Estado Nutricional , Idoso , Biomarcadores , Creatinina , Feminino , Avaliação Geriátrica , Humanos , Masculino , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Fatores de RiscoRESUMO
We examine factors affecting the choice of marketing channels for maize among male, female, and joint decision-making farm households using data from households in Dawuro zone, southern Ethiopia. Econometric results suggest that female and joint decision-makers are more likely to sell maize to consumers or retailers in the main local market where the maize price is higher than to wholesale merchants directly from the farm. Individual decision-makers (male or female) who grow improved maize varieties are more likely to sell to wholesalers directly from the farm. This may be an indication of the effectiveness of joint decisions over individual decisions related to the market price. We also found that improved maize varieties distributed to farmers in the study area are of poor quality and that there is a lack of modern storage facilities so that farmers have to sell immediately after harvest during the lower price season. Thus, there is a need for policies promoting the distribution of high-quality maize seeds and encouraging investments in the establishment of modern maize storage facilities in the study area. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10745-021-00252-x.
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OBJECTIVE: Sarcopenia (especially muscle mass assessed using gold standard techniques) has been suggested as a poorer predictor of mortality than muscle function in patients undergoing hemodialysis. Appropriate methods to estimate muscle mass for use as a good predictor of clinical outcomes remain to be established. We investigated whether the modified creatinine index (mCI), which is a surrogate marker of muscle mass, could predict mortality and cardiovascular (CV) hospitalizations independent of muscle function and other confounders in patients on hemodialysis. DESIGN AND METHODS: In this retrospective study, outpatients (n = 542; mean age, 65.3 years; 60% men; median dialysis vintage, 29 months; mean BMI, 22.0 kg/m2) undergoing hemodialysis were investigated. The mCI, handgrip strength, and gait speed were assessed and related to all-cause mortality and a composite of CV hospitalizations and all-cause mortality. Cox proportional and mixed-effects negative binomial models were fit for mortality and the composite outcomes. RESULTS: Patients were followed up for a median 3 years (interquartile range: 1.5-5.7). Each per SD increase of mCI (HR:0.63, 95% CI:0.62-0.65), handgrip strength (HR:0.51, 95% CI:0.48-0.54), and gait speed (HR:0.60, 95% CI:0.56-0.64) were significantly associated with lower all-cause mortality rates after adjusting for covariates. The mCI was consistently found to be an independent predictor of mortality after additional adjustment for handgrip strength or gait speed. Furthermore, sarcopenic conditions [i.e., lower mCI, and lower handgrip strength (HR:3.79, 95% CI:2.09-6.87) or slower gait speed (HR:4.20, 95% CI:2.38-7.41)] were significantly associated with a higher risk of mortality after adjusting for covariates. Associations of mCI with multiple CV hospitalizations and mortality were similar to those between mCI and mortality. CONCLUSION: The mCI was a good predictor of clinical outcomes and was comparable to muscle function, including handgrip strength and gait speed. The mCI is likely to provide additional diagnostic and prognostic values for sarcopenia in patients on hemodialysis.
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Sarcopenia , Idoso , Creatinina , Feminino , Força da Mão , Humanos , Masculino , Diálise Renal , Estudos Retrospectivos , Sarcopenia/diagnósticoRESUMO
Although vaccination is a particularly important countermeasure against the coronavirus disease 2019 (COVID-19), vaccine hesitancy may be a barrier to an effective vaccination program. It is understood that attitude towards vaccines is not a simple binominal decision between hesitancy and acceptance, but a continuum with a wide range of related factors. It is also likely to change depending on the present situation. Therefore, this study aimed to examine changes in vaccination attitudes across a five-month period during the COVID-19 pandemic and the factors associated with these changes. We conducted a web-based survey with 1000 participants in Japan in September 2021 and examined the relationship between attitudes regarding vaccination and sociodemographic, behavioral, and psychological variables. In addition, we also retrospectively asked for vaccination attitudes as of April 2021. Over the course of five months, we found that vaccine acceptance rates increased from 40.6% to 85.5%. Health-related behaviors such as regular influenza vaccination and medical checkups were consistently associated with vaccine acceptance. Moreover, psychological variables, such as anxiety and risk perception, were associated with changes in vaccination attitudes. As these attitudes can vary depending on time and circumstances, continuous interdisciplinary efforts are required to ensure effective vaccine programs.
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PURPOSE: Most patients receiving hemodialysis have perceived difficulty in mobility tasks, such as basic activities of daily living (ADL), ambulation, and walking up or down stairs, even if they can ambulate independently. Perceived difficulty in performing ADL (ADL difficulty) is reportedly a useful predictor of mortality in older community-dwelling people. However, very few studies have examined the association of ADL difficulty with clinical outcomes in patients receiving hemodialysis. This study aimed to identify the association between ADL difficulty related to mobility tasks of lower limbs and all-cause mortality in patients receiving hemodialysis who are able to ambulate independently. METHODS: This retrospective study analyzed 300 clinically stable outpatients (median age, 65.0 years) receiving hemodialysis. ADL difficulty was evaluated at baseline with a novel questionnaire developed for patients receiving hemodialysis. Lower scores indicated lower ADL, i.e., greater ADL difficulty. The patients were divided into two groups by the median ADL score: a higher ADL group and a lower ADL group. The association between ADL difficulty and all-cause mortality was estimated by Cox regression analyses. RESULTS: Median follow-up duration was 58 months. The incident rates were 0.02 per person-year in the higher ADL group and 0.06 per person-year in the lower ADL group (P < 0.001). After adjusting for the effects of clinical characteristics, the hazard ratio for all-cause mortality in the lower ADL group was 2.70 (95% confidence interval 1.57-4.64) compared with that in the higher ADL group. CONCLUSIONS: Perceived difficulty in mobility tasks was independently associated with all-cause mortality among ambulatory patients receiving hemodialysis.
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Atividades Cotidianas , Extremidade Inferior/fisiopatologia , Diálise Renal/mortalidade , Idoso , Causas de Morte , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
OBJECTIVES: Health-related quality of life (HRQoL) measures capture the patient's experience of the burden of chronic disease and are strongly associated with adverse health-related outcomes across multiple populations. The SF-36 score is the most widely used HRQoL measure among patients with end-stage renal disease. Current understanding of determinants of the physical component summary (PCS) and the mental component summary (MCS) and their association with objectively measured physical performance and activity is limited. METHODS: As an index of HRQoL, we prospectively examined the association of SF-36 and its component scores with physical function among 155 incident dialysis patients from the Hemodialysis Center. We investigated associations of HRQoL with the physical performance-based components of the frailty using multivariate linear and logistic regression after adjustment for confounders. Impaired physical performance was defined as having either slow usual gait speed or weak handgrip strength based on standardized and validated criteria derived from a large cohort study of older adults. RESULTS: The patients had a mean age of 65 ± 11 years, and 52.3% were male. After adjusting confounders, lower PCS was independently associated with decreased physical performance and reduced physical activity, but MCS was not associated. Among the PCS subscales, only physical functioning 10 (PF-10) was consistently associated with outcomes, and every 1 point increase in PF-10 score was associated with 4% lower odds of impaired physical performance (95% confidence interval 2-7, P = .01) after adjustment. CONCLUSIONS: SF-36, especially PF-10, is a valid surrogate that discriminates low physical performance and physical inactivity in the absence of formal physical function testing in patients on hemodialysis. The routine implementation of the PF-10 in clinical care has important clinical implications for medical management and therapeutic decision-making in patients undergoing hemodialysis.
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Fragilidade , Qualidade de Vida , Idoso , Estudos de Coortes , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Desempenho Físico Funcional , Diálise RenalRESUMO
The human genome contains hundreds of large, structurally diverse blocks that are insufficiently represented in the reference genome and are thus not amenable to genomic analyses. Structural diversity in the human population suggests that these blocks are unstable in the germline; however, whether or not these blocks are also unstable in the cancer genome remains elusive. Here we report that the 500 kb block called KRTAP_region_1 (KRTAP-1) on 17q12-21 recurrently demarcates the amplicon of the ERBB2 (HER2) oncogene in breast tumors. KRTAP-1 carries numerous tandemly-duplicated segments that exhibit diversity within the human population. We evaluated the fragility of the block by cytogenetically measuring the distances between the flanking regions and found that spontaneous distance outliers (i.e DNA breaks) appear more frequently at KRTAP-1 than at the representative common fragile site (CFS) FRA16D. Unlike CFSs, KRTAP-1 is not sensitive to aphidicolin. The exonuclease activity of DNA repair protein Mre11 protects KRTAP-1 from breaks, whereas CtIP does not. Breaks at KRTAP-1 lead to the palindromic duplication of the ERBB2 locus and trigger Breakage-Fusion-Bridge cycles. Our results indicate that an insufficiently investigated area of the human genome is fragile and could play a crucial role in cancer genome evolution.
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Neoplasias da Mama/genética , Sítios Frágeis do Cromossomo/genética , Reparo do DNA , Amplificação de Genes , Duplicação Gênica/genética , Genes erbB-2 , Queratinas Específicas do Cabelo/fisiologia , Afidicolina/farmacologia , Mama/metabolismo , Neoplasias da Mama/metabolismo , Células Cultivadas , Instabilidade Cromossômica , Quebras de DNA , Variações do Número de Cópias de DNA , DNA de Neoplasias/genética , Células Epiteliais/metabolismo , Feminino , Variação Genética , Instabilidade Genômica , Humanos , Proteína Homóloga a MRE11/fisiologia , Proteínas de Neoplasias/fisiologia , Sequenciamento Completo do GenomaRESUMO
OBJECTIVE: Patients undergoing hemodialysis (HD) have different physical activity (PA) patterns on HD and non-HD days. Nonetheless, whether these differences are associated with clinical outcomes remains unclear. We examined the association of PA levels on HD and non-HD days with cardiovascular (CV) hospitalizations and mortality. METHODS: Outpatients undergoing HD from 2002 to 2019 were retrospectively enrolled. The number of steps performed over 3 HD days and 4 non-HD days was recorded via accelerometry. Outcomes were all-cause mortality and a composite of CV hospitalizations and mortality. Patients were divided into two groups, each according to the median number of steps performed on HD (2371 steps/day) and non-HD days (3752 steps/day). Further, we categorized them into 4 groups according to each median values: "more active on HD/more active on non-HD (MM)," "more active on HD/less active on non-HD (ML)," "less active on HD/more active on non-HD (LM)," and "less active on HD/less active on non-HD (LL)." Cox and mixed-effects Poisson regression models were used for these outcomes. RESULTS: We analyzed 512 patients (median follow-up, 3.4 years). Higher PA on HD (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.54-0.65), and non-HD (HR, 0.84; 95% CI, 0.80-0.88) was associated with lower mortality risk, respectively. Further, the ML group (HR, 1.20; 95% CI, 1.13-1.28), LM group (HR, 1.82; 95% CI, 1.53-2.17), and LL group (HR, 1.83; 95% CI, 1.65-2.02) had higher mortality risks than the MM group. Associations of PA with multiple CV hospitalizations and mortality were similar to those between PA and mortality. CONCLUSIONS: Higher PA on HD and non-HD days was associated with lower risks of CV hospitalizations and mortality. However, higher PA levels on either HD or non-HD days alone did not improve clinical outcomes.
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Exercício Físico , Diálise Renal , Humanos , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
OBJECTIVE: Neonatal lungs are more tolerant to hyperoxic injury than are adult lungs. This study investigated differences in the response to hyperoxic exposure between neonatal and adult mouse lungs using metabolomics analysis with capillary electrophoresis time-of-flight mass spectrometry (CE- TOFMS). METHODS: Neonatal and adult mice were exposed to 21% or 95% O2 for four days. Subsequently, lung tissue samples were collected and analyzed by CE-TOFMS. Pyruvate dehydrogenase (PDH) enzyme activity was determined using a microplate assay kit. PDH kinase (Pdk) 1, Pdk2, Pdk3, and Pdk4 mRNA expression levels were determined using quantitative reverse transcription-polymerase chain reaction. Pdk4 protein expression was quantified by Western blotting and Pdk4 protein localization was evaluated by immunohistochemistry. RESULTS: Levels of 3-phosphoglyceric acid, 2-phosphoglyceric acid, phosphoenolpyruvic acid, and lactic acid were significantly elevated in the lungs of hyperoxia-exposed versus normoxia-exposed adult mice, whereas no significant differences were observed with hyperoxia exposure in neonatal mice. PDH activity was reduced in the lungs of adult mice only. Pdk4 mRNA expression levels after hyperoxic exposure were significantly elevated in adult mice compared with that in neonatal mice. Conversely, gene expression levels of Pdk1, Pdk2, and Pdk3 did not differ after hyperoxic exposure in either neonatal or adult mice. Pdk4 protein levels were also significantly increased in adult mouse lungs exposed to hyperoxia and were localized mainly to the epithelium of terminal bronchiole. CONCLUSIONS: Specific metabolites associated with glycolysis and gluconeogenesis were altered after hyperoxia exposure in the lungs of adult mice, but not in neonates, which was likely a result of reduced PDH activity due to Pdk4 mRNA upregulation under hyperoxia.
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Hiperóxia/metabolismo , Pulmão/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo , Ácido Pirúvico/metabolismo , Fatores Etários , Animais , Animais Recém-Nascidos , Expressão Gênica , Gluconeogênese , Glicólise , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/metabolismoRESUMO
The areal biomass productivities (g-1 m-2 day-1) of Nannochloropsis oceanica between different sizes of way ponds were compared. Sequential batch cultivation using 2-m2, 20-m2, and 200-m2 raceway ponds with an industrial scale 4000-m2 raceway as the main culture was conducted in summer and autumn during 2017 at Whyalla, Australia. Areal productivities of sequential batch cultivation during the same culture period were 8.4 g ± 0.9 g-1 m-1 day-1 in the 2-m2 ponds, 9.3 g-1 m-1 day-1 in the 20-m2 ponds, and 8.0 g-1 m-1 day-1 in the 200-m2 ponds respectively. In parallel with the operation of the main 4000-m2 pond, some smaller scale ponds of 2, 20, and 200 m2 were operated at the same site under the same conditions. Areal productivity data of dry biomass of Nannochloropsis oceanica in each pond are very similar between industrial 4000-m2 pond and other smaller ponds. In this work, the authors demonstrate that using the growth rate and productivities of Nannochloropsis from smaller scale open ponds with the same depth is valid to estimate for large-scale ponds in excess of 4000 m2.
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Biomassa , Estramenópilas/crescimento & desenvolvimento , Microalgas/crescimento & desenvolvimento , LagoasRESUMO
Coral reefs are currently facing multiple disturbances caused by natural/anthropogenic factors. Recent industrial development might influence reef environments and ecosystems; however, few direct comparisons of coral calcification with the histories of local industries exist. We show the coral Ba/Ca record and growth histories for 46 years collected from Sumiyo Bay, Amami-Oshima Island, Japan. Coral Ba/Ca was mainly controlled by the sediment loads in seawater, which are introduced through the two local rivers. Coral Ba/Ca records have been characterized by two distinct historical periods: the decadal fluctuation corresponding to the traditional silk fabric industry (1960s ~ 1995) and the increasing trend corresponding to the development of quarries and the construction industry (1996 ~). Coral Ba/Ca records and local industrial histories were also linked to coral calcification. A long-term quantitative assessment of reef environments and local industrial changes could provide an evaluation of the survival strategies of reef-building corals in the future.
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Antozoários/fisiologia , Calcificação Fisiológica/fisiologia , Recifes de Corais , Ecossistema , Indústrias , Animais , Antozoários/metabolismo , Conservação dos Recursos Naturais/métodos , Monitoramento Ambiental/métodos , Geografia , Ilhas , Japão , Rios , Estações do Ano , Água do MarRESUMO
Focal copy-number increases (genomic amplification) pinpoint oncogenic driver genes and therapeutic targets in cancer genomes. With the advent of genomic technologies, recurrent genomic amplification has been mapped throughout the genome. Recurrent amplification could be solely due to positive selection for the tumor-promoting effects of amplified gene products. Alternatively, recurrence could result from the susceptibility of the loci to amplification. Distinguishing between these possibilities requires a full understanding of the amplification mechanisms. Two mechanisms, the formation of double minute (DM) chromosomes and breakage-fusion-bridge (BFB) cycles, have been repeatedly linked to genomic amplification, and the impact of both mechanisms has been confirmed in cancer genomics data. We review the details of these mechanisms and discuss the mechanisms underlying recurrence.
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Cromotripsia , Amplificação de Genes , Neoplasias/genética , Animais , Carcinogênese/genética , Linhagem Celular , Quebras de DNA , Variações do Número de Cópias de DNA , Reparo do DNA , Humanos , Oncogenes/genética , Telômero/metabolismoRESUMO
The role of thioredoxin-1 (TRX), a small redox-active protein with antioxidant effects, during hyperoxic lung injury in newborns remains undetermined. We investigated TRX impact on hyperoxic lung injury in newborn TRX transgenic (TRX-Tg) and wildtype (WT) mice exposed to 21% or 95% O2 for four days, after which some mice were allowed to recover in room air for up to 14 days. Lung morphology was assessed by hematoxylin/eosin and elastin staining, as well as immunostaining for macrophages. The gene expression levels of proinflammatory cytokines were evaluated using quantitative real-time polymerase chain reaction. During recovery from hyperoxia, TRX-Tg mice exhibited an improved mean linear intercept length and increased number of secondary septa in lungs compared with the WT mice. Neonatal hyperoxia enhanced the mRNA expression levels of proinflammatory cytokines in the lungs of both TRX-Tg and WT mice. However, interleukin-6, monocyte chemoattractant protein-1, and chemokine (C-X-C motif) ligand 2 mRNA expression levels were reduced in the lungs of TRX-Tg mice compared with the WT mice during recovery from hyperoxia. Furthermore, TRX-Tg mice exhibited reduced macrophage infiltration in lungs during recovery. These results suggest that in newborn mice TRX ameliorates hyperoxic lung injury during recovery likely through the suppression of proinflammatory cytokines.
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BACKGROUND: The arterial oxygen saturation of infants requiring resuscitation can be monitored using a pulse oximeter. However, the device cannot provide information about cerebral oxygenation. Thus, we used a new portable near-infrared spectroscopy (NIRS) device that can monitor regional cerebral tissue oxygen saturation (crSO2) with a probe attached to the examiner's finger. AIM: To identify the reference ranges for crSO2 within the first 10 min after birth in term infants who did not receive any medical intervention in the delivery room. RESULTS: crSO2 in the left frontoparietal area of the forebrain was measured within the first 10 min of life in 127 healthy term infants. The median gestational age and birth weight were 37.6 weeks and 2742 g, respectively, and 85% of the infants were delivered via a scheduled cesarean section. The 3rd-97th percentile values for crSO2 ranged from 33.1% to 56.7% at 1 min, from 33.2% to 59.5% at 2 min, and from 38.7% to 66.6% at 5 min after birth. A median of 3.5 min was required to achieve a crSO2 > 50%. CONCLUSIONS: This study showed the reference ranges for crSO2 measured with the new portable NIRS device within the first 10 min after birth in term infants.
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Encéfalo/irrigação sanguínea , Recém-Nascido/fisiologia , Oximetria/instrumentação , Oxigênio/análise , Espectroscopia de Luz Próxima ao Infravermelho/instrumentação , Feminino , Humanos , Masculino , Oximetria/métodos , Oximetria/normas , Consumo de Oxigênio , Padrões de Referência , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Espectroscopia de Luz Próxima ao Infravermelho/normasRESUMO
RATIONALE & OBJECTIVE: Although a declining body mass index (BMI) is associated with higher mortality in patients on hemodialysis, BMI cannot distinguish lean body mass from fat mass. It remains unclear whether changes over time in lean body mass are associated with mortality. We examined the prognostic significance of changes in the modified creatinine index, a proxy for lean body mass. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Outpatients (n=349; mean age, 67.4 years; 60% men) undergoing maintenance hemodialysis 3 times a week at a treatment center. PREDICTOR: Modified creatinine index and BMI trajectories over a 1-year period. OUTCOMES: All-cause mortality. ANALYTICAL APPROACH: We calculated the percentage of change in modified creatinine index and BMI over a 1-year period. Patients were categorized according to change in modified creatinine index/BMI: no decline (≥0%) or decline (<0%). Kaplan-Meier and Cox proportional hazard analyses were performed to examine whether modified creatinine index and BMI trajectories were associated with mortality. RESULTS: During follow-up (median, 1,157 days), 79 patients died. Decreasing modified creatinine index (HR, 1.31; 95% CI, 1.11-1.54) and BMI (HR, 1.25; 95% CI, 1.01-1.54) over time, measured as continuous variables and expressed per 1-standard deviation decrease, were independently associated with higher risk for all-cause mortality. The decline in modified creatinine index/no decline in BMI group (HR, 2.14; 95% CI, 1.04-4.45) and the decline in modified creatinine index/decline in BMI group (HR, 3.05; 95% CI, 1.58-5.90) had higher rates of mortality compared to the no decline in modified creatinine index/decline in BMI group. LIMITATIONS: The absence of a direct measure of lean body and fat mass and limited generalizability to non-Japanese hemodialysis populations. CONCLUSIONS: The modified creatinine index trajectory is independently associated with mortality and provides additional prognostic information to the BMI trajectory in patients on hemodialysis.