Inflammation-based scores in a large cohort of adrenocortical carcinoma and adrenocortical adenoma: role of the hormonal secretion pattern.

BACKGROUND: Serum inflammation-based scores can predict clinical outcome in several cancer types, including adrenocortical carcinoma (ACC). It is unclear whether the extent of inflammation-based scores alterations in ACC reflects malignancy, steroid excess, or both. METHODS: We investigated a large retrospective cohort of adrenocortical adenomas (ACA, n = 429) and ACC (n = 61) with available baseline full blood count and hormonal evaluation. We examined the relationship between different inflammation-based scores [neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), and prognostic nutrition index (PNI)] and both malignancy and steroid secretion patterns. RESULTS: All inflammation-based scores differed between ACC and ACA: patients with ACC had higher NLR, PLR, SII and lower LMR and PNI levels compared to ACA (all p values < 0.001). NLR showed a positive correlation with cortisol levels after overnight 1 mg-dexamethasone suppression test (1 mg-DST), both in ACC and ACA (p < 0.01). The ROC curve analysis determined NLR > 2.6 as the best cut-off to discriminate ACC from ACA [AUC = 0.846, p < 0.01]. At multivariable analysis, NLR > 2.6 was independently associated with ACC, 1 mg-DST cortisol levels and age, but not with tumour size. Considering the ACC, NLR and SII were higher and PNI was lower in patients with cortisol excess compared to those without cortisol excess (p = 0.002, p = 0.007, and p = 0.044 respectively). Finally, LMR and NLR differed between inactive-ACC (n = 10) and inactive-ACA (n = 215) (p = 0.040 and p = 0.031, respectively). CONCLUSION: Inflammation-based scores are related to steroid secretion both in ACC and ACA. ACCs present a higher grade of inflammation regardless of their hormonal secretion, likely as a feature of malignancy itself.

Inflammation dynamically regulates steroid hormone metabolism and action within macrophages in rheumatoid arthritis.

RATIONALE: In inflammatory diseases such as rheumatoid arthritis (RA), steroid metabolism is a central component mediating the actions of immuno-modulatory glucocorticoids and sex steroids. However, the regulation and function of cellular steroid metabolism within key leukocyte populations such as macrophages remain poorly defined. In this study, the inflammatory regulation of global steroid metabolism was assessed in RA macrophages. METHODS: Bulk RNA-seq data from RA synovial macrophages was used to assess transcripts encoding key enzymes in steroid metabolism and signalling. Changes in metabolism were assessed in synovial fluids, correlated to measures of disease activity and functionally validated in primary macrophage cultures. RESULTS: RNA-seq revealed a unique pattern of differentially expressed genes, including changes in genes encoding the enzymes 11ß-HSD1, SRD5A1, AKR1C2 and AKR1C3. These correlated with disease activity, favouring increased glucocorticoid and androgen levels. Synovial fluid 11ß-HSD1 activity correlated with local inflammatory mediators (TNFα, IL-6, IL-17), whilst 11ß-HSD1, SRD5A1 and AKR1C3 activity correlated with systemic measures of disease and patient pain (ESR, DAS28 ESR, global disease activity). Changes in enzyme activity were evident in inflammatory activated macrophages in vitro and revealed a novel androgen activating role for 11ß-HSD1. Together, increased glucocorticoids and androgens were able to suppress inflammation in macrophages and fibroblast-like-synoviocytes. CONCLUSIONS: This study underscores the significant increase in androgen and glucocorticoid activation within inflammatory polarized macrophages of the synovium, contributing to local suppression of inflammation. The diminished profile of inactive steroid precursors in postmenopausal women may contribute to disturbances in this process, leading to increased disease incidence and severity.

Anthropogenic, biogenic, and photochemical influences on surface formaldehyde and its significant decadal (2006-2017) decrease in the Lewiston-Clarkston valley of the northwestern United States.

Formaldehyde (HCHO) is a key carcinogen and plays an important role in atmospheric chemistry. Both field measurements and Positive Matrix Factorization (PMF) modeling have been employed to investigate the concentrations and sources of HCHO in the Lewiston-Clarkston (LC) valley of the mountainous northwestern U.S. Different instruments were deployed to measure surface formaldehyde and other related compounds in July of 2016 and 2017. The measurements reveal that the average HCHO concentrations have significantly decreased to 2-5 ppb in the LC valley in comparison to its levels (10-20 ppb) observed in July 2006. This discovery with surface measurements deserves attention given that satellite retrievals showed an increasing long-term trend from 2005 to 2014 in total vertical column density of HCHO in the region, suggesting that satellite instruments may not adequately resolve small valleys in the mountainous region. Our PMF modeling identified four major sources of HCHO in the valley: (1) emissions from a local paper mill, (2) secondary formation and background, (3) biogenic sources, and (4) traffic. This study reveals that the emissions from the paper mill cause high HCHO spikes (6-19 ppb) in the early morning. It is found that biogenic volatile organic compounds (VOCs) in the area are influenced by national forests surrounding the region (e.g., Nez Perce-Clearwater, Umatilla, Wallowa-Whitman, and Idaho Panhandle National Forests). The results provide useful information for developing strategies to control HCHO levels and have implications for future HCHO studies in atmospheric chemistry, which affects secondary aerosols and ozone formation.

Fire safety and emergency evacuation guidelines for intensive care units and operating theatres: for use in the event of fire, flood, power cut, oxygen supply failure, noxious gas, structural collapse or other critical incidents: Guidelines from the Association of Anaesthetists and the Intensive Care Society.

The need to evacuate an ICU or operating theatre complex during a fire or other emergency is a rare event but one potentially fraught with difficulty: Not only is there a risk that patients may come to harm but also that staff may be injured and unable to work. Designing newly-built or refurbished ICUs and operating theatre suites is an opportunity to incorporate mandatory fire safety features and improve the management and outcomes of such emergencies: These include well-marked manual fire call points and oxygen shut off valves (area valve service units); the ability to isolate individual zones; multiple clear exit routes; small bays or side rooms; preference for ground floor ICU location and interconnecting routes with operating theatres; separate clinical and non-clinical areas. ICUs and operating theatre suites should have a bespoke emergency evacuation plan and route map that is readily available. Staff should receive practical fire and evacuation training in their clinical area of work on induction and annually as part of mandatory training, including 'walk-through practice' or simulation training and location of manual fire call points and fire extinguishers, evacuation routes and location and operation of area valve service units. The staff member in charge of each shift should be able to select and operate fire extinguishers and lead an evacuation. Following an emergency evacuation, a network-wide response should be activated, including retrieval and transport of patients to other ICUs if needed. A full investigation should take place and ongoing support and follow-up of staff provided.

Changes over time in latent patterns of childhood-to-adulthood BMI development in Great Britain: evidence from three cohorts born in 1946, 1958, and 1970.

BACKGROUND: Most studies on secular trends in body mass index (BMI) are cross-sectional and the few longitudinal studies have typically only investigated changes over time in mean BMI trajectories. We aimed to describe how the evolution of the obesity epidemic in Great Britain reflects shifts in the proportion of the population demonstrating different latent patterns of childhood-to-adulthood BMI development. METHODS: We used pooled serial BMI data from 25,655 participants in three British cohorts: the 1946 National Survey of Health and Development (NSHD), 1958 National Child Development Study (NCDS), and 1970 British Cohort Study (BCS). Sex-specific growth mixture models captured latent patterns of BMI development between 11 and 42 years. The classes were characterised in terms of their birth cohort composition. RESULTS: The best models had four classes, broadly similar for both sexes. The 'lowest' class (57% of males; 47% of females) represents the normal weight sub-population, the 'middle' class (16%; 15%) represents the sub-population who likely develop overweight in early/mid-adulthood, and the 'highest' class (6%; 9%) represents those who likely develop obesity in early/mid-adulthood. The remaining class (21%; 29%) reflects a sub-population with rapidly 'increasing' BMI between 11 and 42 years. Both sexes in the 1958 NCDS had greater odds of being in the 'highest' class compared to their peers in the 1946 NSHD but did not have greater odds of being in the 'increasing' class. Conversely, males and females in the 1970 BCS had 2.78 (2.15, 3.60) and 1.87 (1.53, 2.28), respectively, times higher odds of being in the 'increasing' class. CONCLUSIONS: Our results suggest that the obesity epidemic in Great Britain reflects not only an upward shift in BMI trajectories but also a more recent increase in the number of individuals demonstrating more rapid weight gain, from normal weight to overweight, across the second, third, and fourth decades of life.

Novel DNA methylation signatures of tobacco smoking with trans-ethnic effects.

BACKGROUND: Smoking remains one of the leading preventable causes of death. Smoking leaves a strong signature on the blood methylome as shown in multiple studies using the Infinium HumanMethylation450 BeadChip. Here, we explore novel blood methylation smoking signals on the Illumina MethylationEPIC BeadChip (EPIC) array, which also targets novel CpG-sites in enhancers. METHOD: A smoking-methylation meta-analysis was carried out using EPIC DNA methylation profiles in 1407 blood samples from four UK population-based cohorts, including the MRC National Survey for Health and Development (NSHD) or 1946 British birth cohort, the National Child Development Study (NCDS) or 1958 birth cohort, the 1970 British Cohort Study (BCS70), and the TwinsUK cohort (TwinsUK). The overall discovery sample included 269 current, 497 former, and 643 never smokers. Replication was pursued in 3425 trans-ethnic samples, including 2325 American Indian individuals participating in the Strong Heart Study (SHS) in 1989-1991 and 1100 African-American participants in the Genetic Epidemiology Network of Arteriopathy Study (GENOA). RESULTS: Altogether 952 CpG-sites in 500 genes were differentially methylated between smokers and never smokers after Bonferroni correction. There were 526 novel smoking-associated CpG-sites only profiled by the EPIC array, of which 486 (92%) replicated in a meta-analysis of the American Indian and African-American samples. Novel CpG sites mapped both to genes containing previously identified smoking-methylation signals and to 80 novel genes not previously linked to smoking, with the strongest novel signal in SLAMF7. Comparison of former versus never smokers identified that 37 of these sites were persistently differentially methylated after cessation, where 16 represented novel signals only profiled by the EPIC array. We observed a depletion of smoking-associated signals in CpG islands and an enrichment in enhancer regions, consistent with previous results. CONCLUSION: This study identified novel smoking-associated signals as possible biomarkers of exposure to smoking and may help improve our understanding of smoking-related disease risk.

Life course longitudinal growth and risk of knee osteoarthritis at age 53 years: evidence from the 1946 British birth cohort study.

OBJECTIVE: To examine the relationship between height gain across childhood and adolescence with knee osteoarthritis in the MRC National Survey of Health and Development (NSHD). MATERIALS AND METHODS: Data are from 3035 male and female participants of the NSHD. Height was measured at ages 2, 4, 6, 7, 11 and 15 years, and self-reported at ages 20 years. Associations between (1) height at each age (2) height gain during specific life periods (3) Super-Imposition by Translation And Rotation (SITAR) growth curve variables of height size, tempo and velocity, and knee osteoarthritis at 53 years were tested. RESULTS: In sex-adjusted models, estimated associations between taller height and decreased odds of knee osteoarthritis at age 53 years were small at all ages - the largest associations were an OR of knee osteoarthritis of 0.9 per 5 cm increase in height at age 4, (95% CI 0.7-1.1) and an OR of 0.9 per 5 cm increase in height, (95% CI 0.8-1.0) at age 6. No associations were found between height gain during specific life periods or the SITAR growth curve variables and odds of knee osteoarthritis. CONCLUSIONS: There was limited evidence to suggest that taller height in childhood is associated with decreased odds of knee osteoarthritis at age 53 years in this cohort. This work enhances our understanding of osteoarthritis predisposition and the contribution of life course height to this.

A Sharing Meanings Approach for Interdisciplinary Hazards Research.

Hazards researchers frequently examine complex socioenvironmental problems, a difficult undertaking that is further compounded by the challenge of navigating the many disciplinary approaches in the field. This article draws on key insights from studies of the interdisciplinary process and proposes the "sharing meanings approach" for improving interdisciplinary collaboration in hazards research. The sharing meanings approach addresses common challenges to interdisciplinary teamwork and organizes them into four focal areas: (1) worldviews (including ontological, epistemological, and philosophical perspectives), (2) language, (3) research design, and (4) project goals. The approach emphasizes the process of sharing rather than seeking to develop a single set of shared meanings related to the four focal areas. The article identifies common challenges and recommends strategies and actions within each focal area for guiding teams toward sharing their implicit meanings. A hypothetical example is introduced to demonstrate how the approach offers a path for revealing and overcoming the common roadblocks experienced in interdisciplinary hazards research. By making interdisciplinary hazards teams' implicit assumptions explicit, the sharing meanings approach offers an operational process to seize on moments of difference as productive tension and to see such challenges as opportunities-rather than obstacles-for innovating toward hybrid methodological research designs in hazards research.

11ß-HSD1 plays a critical role in trabecular bone loss associated with systemic glucocorticoid therapy.

BACKGROUND: Despite their efficacy in the treatment of chronic inflammation, the prolonged application of therapeutic glucocorticoids (GCs) is limited by significant systemic side effects including glucocorticoid-induced osteoporosis (GIOP). 11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is a bi-directional enzyme that primarily activates GCs in vivo, regulating tissue-specific exposure to active GC. We aimed to determine the contribution of 11ß-HSD1 to GIOP. METHODS: Wild type (WT) and 11ß-HSD1 knockout (KO) mice were treated with corticosterone (100 µg/ml, 0.66% ethanol) or vehicle (0.66% ethanol) in drinking water over 4 weeks (six animals per group). Bone parameters were assessed by micro-CT, sub-micron absorption tomography and serum markers of bone metabolism. Osteoblast and osteoclast gene expression was assessed by quantitative RT-PCR. RESULTS: Wild type mice receiving corticosterone developed marked trabecular bone loss with reduced bone volume to tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N). Histomorphometric analysis revealed a dramatic reduction in osteoblast numbers. This was matched by a significant reduction in the serum marker of osteoblast bone formation P1NP and gene expression of the osteoblast markers Alp and Bglap. In contrast, 11ß-HSD1 KO mice receiving corticosterone demonstrated almost complete protection from trabecular bone loss, with partial protection from the decrease in osteoblast numbers and markers of bone formation relative to WT counterparts receiving corticosterone. CONCLUSIONS: This study demonstrates that 11ß-HSD1 plays a critical role in GIOP, mediating GC suppression of anabolic bone formation and reduced bone volume secondary to a decrease in osteoblast numbers. This raises the intriguing possibility that therapeutic inhibitors of 11ß-HSD1 may be effective in preventing GIOP in patients receiving therapeutic steroids.

Therapeutic glucocorticoids prevent bone loss but drive muscle wasting when administered in chronic polyarthritis.

BACKGROUND: Patients with rheumatoid arthritis (RA) experience extra-articular manifestations including osteoporosis and muscle wasting, which closely associate with severity of disease. Whilst therapeutic glucocorticoids (GCs) reduce inflammation in RA, their actions on muscle and bone metabolism in the context of chronic inflammation remain unclear. We utilised the TNF-tg model of chronic polyarthritis to ascertain the impact of therapeutic GCs on bone and muscle homeostasis in the context of systemic inflammation. METHODS: TNF-tg and wild-type (WT) animals received either vehicle or the GC corticosterone (100 µg/ml) in drinking water at onset of arthritis. Arthritis severity and clinical parameters were measured, serum collected for ELISA and muscle and bone biopsies collected for µCT, histology and mRNA analysis. In vivo findings were examined in primary cultures of osteoblasts, osteoclasts and myotubes. RESULTS: TNF-tg mice receiving GCs showed protection from inflammatory bone loss, characterised by a reduction in serum markers of bone resorption, osteoclast numbers and osteoclast activity. In contrast, muscle wasting was markedly increased in WT and TNF-tg animals receiving GCs, independently of inflammation. This was characterised by a reduction in muscle weight and fibre size, and an induction in anti-anabolic and catabolic signalling. CONCLUSIONS: This study demonstrates that when given in early onset chronic polyarthritis, oral GCs partially protect against inflammatory bone loss, but induce marked muscle wasting. These results suggest that in patients with inflammatory arthritis receiving GCs, the development of interventions to manage deleterious side effects in muscle should be prioritised.

Explaining differential vulnerability to climate change: A social science review.

The varied effects of recent extreme weather events around the world exemplify the uneven impacts of climate change on populations, even within relatively small geographic regions. Differential human vulnerability to environmental hazards results from a range of social, economic, historical, and political factors, all of which operate at multiple scales. While adaptation to climate change has been the dominant focus of policy and research agendas, it is essential to ask as well why some communities and peoples are disproportionately exposed to and affected by climate threats. The cases and synthesis presented here are organized around four key themes (resource access, governance, culture, and knowledge), which we approach from four social science fields (cultural anthropology, archaeology, human geography, and sociology). Social scientific approaches to human vulnerability draw vital attention to the root causes of climate change threats and the reasons that people are forced to adapt to them. Because vulnerability is a multidimensional process rather than an unchanging state, a dynamic social approach to vulnerability is most likely to improve mitigation and adaptation planning efforts. This article is categorized under:Vulnerability and Adaptation to Climate Change > Values-Based Approach to Vulnerability and Adaptation.

Childhood adversity and DNA methylation in two population-based cohorts.

Childhood adversity affects later health, but the underlying molecular mechanisms are unclear. Although there is some evidence from animal models and case-control studies of a role for DNA methylation, evidence from human population-based studies is limited. In two cohorts (mothers from the Avon Longitudinal Study of Parents and Children, ALSPAC, n = 780 and women from the MRC National Survey of Health and Development, NSHD, n = 552), we assessed the association of seven adverse childhood experiences (ACEs: parental physical illness, parental mental illness, parental death, parental separation, suboptimal maternal bonding, childhood illness and child maltreatment) as well as their combination (ACE score) with genome-wide DNA methylation levels measured using the Illumina Infinium HumanMethylation450 BeadChip in peripheral blood at mean age 47 years (ALSPAC) and in buccal cells at age 53 years (NSHD). CpG sites with a genome-wide false discovery rate (FDR) below 0.05 and differentially methylated regions (DMRs) with one-step Sidák correction p-values below 0.05 in each cohort were examined in the other cohort. No individual CpG sites replicated across cohorts. However, nine DMRs replicated across cohorts respectively associated with the ACE score (one region), parental mental illness (two regions), parental physical illness (three regions) and parental death (three regions). These observations indicate that some adverse childhood experiences, notably those related to parental health, may leave imprints on peripheral DNA methylation that persist to mid-life.

Evaluating the success of public participation in integrated catchment management.

Recognition of the need to manage the water environment in more holistic ways has resulted in the global growth of Integrated Catchment Management (ICM). ICM is characterised by horizontal integration, encouraging interdisciplinary working between traditionally disparate management sectors, alongside vertical integration, characterised by the engagement of communities; central is the promotion of participatory governance and management decision-making. ICM has been translated into policy through, for example, the EU Water Framework Directive and at a national level by policies such as the Catchment Based Approach in England. Research exploring the implementation of these policies has reported success at a catchment level, but further research is required to explore practices of management at local level within catchments. This paper presents the findings of participatory research undertaken with a catchment partnership in the northeast of England to explore the integration of top-down policy translation with how local communities interact with management agencies at sub-catchment scale (a bottom-up perspective). The research found that supra-catchment scale drivers dominate the vertical interplay between management systems at more local levels. These drivers embed traditional practices of management, which establishes public participation as a barrier to delivery of top-down management objectives, resulting in practices that exclude communities and participatory movements at the local level. Although collaboration between agencies at the partnership scale offers a potential solution to overcoming these obstacles, the paper recommends changes to supra-catchment governance structures to encourage flexibility in developing local participatory movements as assets. Further research is necessary to develop new practices of management to integrate local people more effectively into the management process.

11 Beta-hydroxysteroid dehydrogenase type 1 regulates synovitis, joint destruction, and systemic bone loss in chronic polyarthritis.

OBJECTIVE: In rheumatoid arthritis, the enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is highly expressed at sites of inflammation, where it converts inactive glucocorticoids (GC) to their active counterparts. In conditions of GC excess it has been shown to be a critical regulator of muscle wasting and bone loss. Here we examine the contribution of 11ß-HSD1 to the pathology of persistent chronic inflammatory disease. METHODS: To determine the contribution of 11ß-HSD1 to joint inflammation, destruction and systemic bone loss associated with persistent inflammatory arthritis, we generated mice with global and mesenchymal specific 11ß-HSD1 deletions in the TNF-transgenic (TNF-tg) model of chronic polyarthritis. Disease severity was determined by clinical scoring. Histology was assessed in formalin fixed sections and fluorescence-activated cell sorting (FACS) analysis of synovial tissue was performed. Local and systemic bone loss were measured by micro computed tomography (micro-CT). Measures of inflammation and bone metabolism were assessed in serum and in tibia mRNA. RESULTS: Global deletion of 11ß-HSD1 drove an enhanced inflammatory phenotype, characterised by florid synovitis, joint destruction and systemic bone loss. This was associated with increased pannus invasion into subchondral bone, a marked polarisation towards pro-inflammatory M1 macrophages at sites of inflammation and increased osteoclast numbers. Targeted mesenchymal deletion of 11ß-HSD1 failed to recapitulate this phenotype suggesting that 11ß-HSD1 within leukocytes mediate its protective actions in vivo. CONCLUSIONS: We demonstrate a fundamental role for 11ß-HSD1 in the suppression of synovitis, joint destruction, and systemic bone loss. Whilst a role for 11ß-HSD1 inhibitors has been proposed for metabolic complications in inflammatory diseases, our study suggests that this approach would greatly exacerbate disease severity.

Chemical Characterization and Source Apportionment of PM2.5 in a Nonattainment Rocky Mountain Valley.

Severe air pollution has significant adverse health effects and poses a threat to public health in many communities, including nonattainment areas in the Unites States. To develop effective control strategies to reduce air pollution with minimum economic cost, one of the biggest challenges is to quantify the contributions from different sources. By combining chemical analyses, Positive Matrix Factorization modeling, and emission inventory development, this study identified primary and secondary sources of particulate matter with a diameter of <2.5 µm (PM) in a nonattainment Rocky Mountain valley (i.e., West Silver Valley [WSV]) in Idaho. The results show that biomass burning is the dominant source and contributes ∼84% of the PM concentration in the valley. The study also identified influences on the WSV PM concentrations from traffic (7.4%), soil dust (3.4%), and secondary aerosols (4.8%). The results of this paper represent the first report on the chemical composition and source apportionment of PM in mountain valleys of northern Idaho and have been used to develop effective strategies to reduce the PM concentrations in the WSV. Moreover, this study provides detailed equations and methods in PM speciation, accounting for artifacts of the chemical analysis, Positive Matrix Factorization modeling, and emission inventory development, which can be used for source apportionment of severe air pollution in other regions.

Effect of supplementation of phytase to diets low in inorganic phosphorus on growth performance and mineralization of broilers.

There has been discussion regarding microbial phytase replacing inorganic phosphorus (P) supplementation in broiler diets. Therefore, an experiment was conducted to examine the effect of phytase supplementation on diets low in inorganic P. Ross 308 broilers (n = 288) were fed one of 6 experimental diets in 4 phases. The control diet had 16.20, 10.90, 9.40, and 6.10 g/kg inorganic P in the Starter, Grower 1, Grower 2 and Finisher phase respectively. The remaining diets had 10.50 g/kg inorganic P in the Starter phase. Two of the diets had graded reductions in inorganic P of 5.10, 3.60, and 0.60 g/kg or 2.00, 0.50, and 0.60 g/kg for the Grower 1, Grower 2 and Finisher phase respectively, plus 500 FTU phytase. Three of the diets had inorganic P levels of 0.40, 0.50, and 0.60 g/kg for the Grower 1, Grower 2 and Finisher diets respectively and either 500, 750, or 1,000 FTU phytase. Broiler performance was analyzed at d 10, 20, 26, and 35. On d 35, ileal calcium (Ca) and P digestibility and tibia bone strength, mineralization, and mineral content were analyzed. There were no significant differences between the control diet and diet containing 1,000 FTU phytase and low inorganic P in the grower or finisher diets based on bird performance, tibia strength, and Ca and P digestibility. Birds fed the control diet had significantly higher BWG (P = 0.001), bone strength (P < 0.001) and ash content (P < 0.001) compared to birds fed the diets with 500 FTU or 750 FTU phytase and low inorganic P in the grower and finisher stages. This may be due to incomplete dephosphorylation of the inositol ring of phytate with these doses of phytase, but with 1,000 FTU phytase there was almost complete phosphate hydrolysis of each phytate. This study showed that relying on phytase alone to ensure full supply of P in broiler diets is viable in finisher diets but is not recommended in grower diets unless phytase is supplied at doses of 1,000 FTU or greater.

Early menarche and blood pressure in adulthood: systematic review and meta-analysis.

Background: It has been reported that early menarche is associated with high blood pressure and hypertension. However, some studies have failed to observe such association. We carried out a systematic review and meta-analysis on the association of early menarche with hypertension and high blood pressure in adulthood. Methods: PUBMED, SciELO, Scopus and LILACS databases were searched. Studies that evaluated the association of early menarche with hypertension or high blood pressure, among women aged 20 years or more were included. Random effects models were used to pool the estimates. Meta-regression was used to evaluate the contribution of different co-variables to heterogeneity. Results: We identified 17 studies with 18 estimates on the association of early menarche with hypertension and high blood pressure. The odds of hypertension/high blood pressure was higher among women with early menarche [pooled (OR):1.25; 95% confidence interval (CI): 1.17-1.34; P < 0.001]. In the meta-regression analysis, studies evaluating 1500 subjects or more had a higher pooled OR [1.27; 95%CI (1.19;1.36)] than those with less participants. Although funnel plots showed some asymmetry, Egger tests were not statistically significant. Therefore, it is unlikely that the observed association was to publication bias. Conclusions: Early menarche is associated with hypertension among adult woman.