The Gut Microbiota in the First Decade of Life

Appreciation of the importance of the gut microbiome is growing, and it is becoming increasingly relevant to identify preventive or therapeutic solutions targeting it. The composition and function of the gut microbiota are relatively well described for infants (less than 3 years) and adults, but have been largely overlooked in pre-school (3-6 years) and primary school-age (6-12 years) children, as well as teenagers (12-18 years). Early reports suggested that the infant microbiota would attain an adult-like structure at the age of 3 years, but recent studies have suggested that microbiota development may take longer. This development time is of key importance because there is evidence to suggest that deviations in this development may have consequences in later life. In this review, we provide an overview of current knowledge concerning the gut microbiota, its evolution, variation, and response to dietary challenges during the first decade of life with a focus on healthy pre-school and primary school-age children (up to 12 years) from various populations around the globe. This knowledge should facilitate the identification of diet-based approaches targeting individuals of this age group, to promote the development of a healthy microbiota in later life.Peer reviewe

Transient genome-wide interactions of the master transcription factor NLP7 initiate a rapid nitrogen-response cascade

Dynamic reprogramming of gene regulatory networks (GRNs) enables organisms to rapidly respond to environmental perturbation. However, the underlying transient interactions between transcription factors (TFs) and genome-wide targets typically elude biochemical detection. Here, we capture both stable and transient TF-target interactions genome-wide within minutes after controlled TF nuclear import using time-series chromatin immunoprecipitation (ChIP-seq) and/or DNA adenine methyltransferase identification (DamID-seq). The transient TF-target interactions captured uncover the early mode-of-action of NIN-LIKE PROTEIN 7 (NLP7), a master regulator of the nitrogen signaling pathway in plants. These transient NLP7 targets captured in root cells using temporal TF perturbation account for 50% of NLP7-regulated genes not detectably bound by NLP7 in planta. Rapid and transient NLP7 binding activates early nitrogen response TFs, which we validate to amplify the NLP7-initiated transcriptional cascade. Our approaches to capture transient TF-target interactions genome-wide can be applied to validate dynamic GRN models for any pathway or organism of interest. Conventional methods cannot reveal transient transcription factors (TFs) and targets interactions. Here, Alvarez et al. capture both stable and transient TF-target interactions by time-series ChIP-seq and/or DamID-seq in a cell-based TF perturbation system and show NLP7 as a master TF to initiate a rapid nitrogen-response cascade

Factors Associated With Access to HIV Testing and Primary Care Among Migrants Living in Europe: Cross-Sectional Survey

BACKGROUND: There is a heavy and disproportionate burden of human immunodeficiency virus (HIV) infection among migrant communities living in Europe. Despite this, the published evidence related to HIV testing, prevention, and treatment needs for migrants is sparse. OBJECTIVE: The aim of this study was to identify the factors associated with access to primary care and HIV testing among migrant groups living in Europe. METHODS: A Web-based survey (available in 14 languages) was open to all people aged 18 years and older, living outside their country of birth in the World Health Organization (WHO) European area. Community organizations in 9 countries promoted the survey to migrant groups, focusing on those at a higher risk of HIV (sub-Saharan Africans, Latin Americans, gay or bisexual men, and people who inject drugs). Multivariable analysis examined factors associated with access to primary care and previous history of an HIV test. RESULTS: In total, 559 women, 395 heterosexual men, and 674 gay or bisexual men were included in the analysis, and 68.1% (359/527) of women, 59.5% (220/371) of heterosexual men, and 89.6% (596/664) of gay or bisexual men had tested for HIV. Low perceived risk was the reason given for not testing by 62.3% (43/69) of gay or bisexual men and 83.3% (140/168) of women and heterosexual men who reported never having tested for HIV. Access to primary care was >60% in all groups. Access to primary care was strongly positively associated with living in Northern Europe compared with Southern Europe (women: adjusted odds ratio, aOR 34.56 [95% CI 11.58-101]; heterosexual men: aOR 6.93 [95% CI 2.49-19.35], and gay or bisexual men: aOR 2.53 [95% CI 1.23-5.19]), whereas those with temporary residency permits were less likely to have access to primary care (women: aOR 0.41 [95% CI 0.21-0.80] and heterosexual men: aOR 0.24 [95% CI 0.10-0.54] only). Women who had experience of forced sex (aOR 3.53 [95% CI 1.39-9.00]) or postmigration antenatal care (aOR 3.07 [95% CI 1.55-6.07]) were more likely to have tested for HIV as were heterosexual men who had access to primary care (aOR 3.13 [95% CI 1.58-6.13]) or reported "Good" health status (aOR 2.94 [95% CI 1.41-5.88]). CONCLUSIONS: Access to primary care is limited by structural determinants such as immigration and health care policy, which varies across Europe. For those migrants who can access primary care and other health services, missed opportunities for HIV testing remain a barrier to earlier testing and diagnosis for migrants in Europe. Clinicians should be aware of these potential structural barriers to HIV testing as well as low perception of HIV risk in migrant groups.This project received funding from the European Union’s Seventh Framework Programme for research, technological development, and demonstration under EuroCoord grant agreement number 260694. IF was funded by a Doctoral Research Fellowship from the National Institute for Health Research (NIHR). The views expressed in this paper are those of the authors and not necessarily those of the National Health Service (NHS), the National Institute for Health Research (NIHR), or the Department of Health. Additional funding was received from Gilead Sciences Europe Ltd; NIHR Clinical Research Network, the United Kingdom; Foundation for AIDS Research and Prevention in Spain (FISPSE) Project 361036/10; Consortium of Biomedical Research in Epidemiology and Public Health, Spain; Spanish HIV Research Network for Excellence (RD06/006 and RD12/0017/0018); Research and Development Fund, Public Health Service of Amsterdam; and the Swiss HIV Cohort Study (project #727), supported by the Swiss National Science Foundation (grant #148522) and by the Swiss HIV Cohort Study research foundation. No funder had any role in the study, writing of the manuscript, or decision to submit for publication.S

State of the Science of Scale-Up of Cancer Prevention and Early Detection interventions in Low- and Middle-income Countries: a Scoping Review

PURPOSE: Cancer deaths in low- and middle-income countries (LMICs) will nearly double by 2040. Available evidence-based interventions (EBIs) for cancer prevention and early detection can reduce cancer-related mortality, yet there is a lack of evidence on effectively scaling these EBIs in LMIC settings. METHODS: We conducted a scoping review to identify published literature from six databases between 2012 and 2022 that described efforts for scaling cancer prevention and early detection EBIs in LMICs. Included studies met one of two definitions of scale-up: (1) deliberate efforts to increase the impact of effective intervention to benefit more people or (2) an intervention shown to be efficacious on a small scale expanded under real-world conditions to reach a greater proportion of eligible population. Study characteristics, including EBIs, implementation strategies, and outcomes used, were summarized using frameworks from the field of implementation science. RESULTS: This search yielded 3,076 abstracts, with 24 studies eligible for inclusion. Included studies focused on a number of cancer sites including cervical (67%), breast (13%), breast and cervical (13%), liver (4%), and colon (4%). Commonly reported scale-up strategies included developing stakeholder inter-relationships, training and education, and changing infrastructure. Barriers to scale-up were reported at individual, health facility, and community levels. Few studies reported applying conceptual frameworks to guide strategy selection and evaluation. CONCLUSION: Although there were relatively few published reports, this scoping review offers insight into the approaches used by LMICs to scale up cancer EBIs, including common strategies and barriers. More importantly, it illustrates the urgent need to fill gaps in research to guide best practices for bringing the implementation of cancer EBIs to scale in LMICs

American political affiliation, 2003–43: a cohort component projection

The recent rise and stability in American party identification has focused interest on the long-term dynamics of party bases. Liberal commentators cite immigration and youth as forces which will produce a natural Democratic advantage in the future while conservative writers highlight the importance of high Republican fertility in securing Republican growth. These concerns foreground the neglect of demography within political science. This paper addresses this omission by conducting the first ever cohort component projection of American partisan populations to 2043 based on survey and census data. A number of scenarios are modeled, but, on current trends, we predict that American partisanship will shift much less than the nation’s ethnic composition because the parties’ age structures are similar. Still, our projections find that the Democrats gain two to three percentage points from the Republicans by 2043, mainly through immigration, though Republican fertility may redress the balance in the very long term

Prevalence and risk factors of brucellosis among febrile patients attending a community hospital in south western Uganda

Human brucellosis, a chronic disease contracted through contact with animals and consuption of unpasteurized dairy products is underreported in limited-resource countries. This cross-sectional study aimed to determine the prevalence and risk factors of brucellosis among febrile patients attending a community hospital in South western Uganda. A questionnaire that captured socio-demographic, occupational and clinical data was administered. Blood samples were tested for Brucella antibodies using Rose Bengal Plate Test (RBPT) and blood culture with standard aerobic BACTEC bottle was done. Of 235 patients enrolled, prevalence of brucellosis (RBPT or culture confirmed) was 14.9% (95%CI 10.6-20.1) with a culture confrmation in 4.3% of the participants. The factors independently associated with brucellosis were consumption of raw milk (aOR 406.15, 95% CI 47.67-3461.69); history of brucellosis in the family (aOR 9.19, 95% CI 1.98-42.54); and selling hides and skins (aOR 162.56, 95% CI 2.86-9256.31). Hepatomegaly (p < 0.001), splenomegaly (p = 0.018) and low body mass index (p = 0.032) were more common in patients with brucellosis compared to others. Our findings reveal a high prevalence of brucellosis among febrile patients and highlight a need for implementing appropiate tests, public awareness activities and vaccination of animals to control and eliminate the disease

Deliverable D4.4-5: Precision and behaviour of fish-based ecological quality metrics in relation to natural and anthropogenic pressure gradients in European estuaries and lagoons

This report summarises the work conducted in Work Package 4.4 – BQE fish in transitional (i.e. estuarine and lagoon) waters (TW) within the project WISER under the sponsorship of the European Commission. It omits most technical details of the analyses given in the four previous Work Package reports, but still provides the necessary information to understand the rationale, approach and underlying assumptions necessary to discuss the results. The focus is therefore to discuss and integrate the results obtained within Work Package 4.4 and with this, make recommendations to improve fish-based ecological assessments in TW, principally estuaries and lagoons. In addition, and to assist with the WFD implementation which is the overarching theme of WISER, the deliverable includes, where appropriate, case studies where we have used multi-metric fish indices currently under development, or already in use for WFD compliance monitoring across Europe. Furthermore, results of the work package have been shared with relevant Geographical Intercalibration Groups (GIGs) supporting the harmonization and equalization process across transitional fish indices in Europe. Development strategies for fish indices in TW vary but generally include: (1) the calibration of metrics to anthropogenic pressures, (2) the development of reference conditions, (3) the calculation of ecological quality ratios, and (4) the designation of thresholds for Ecological Status (ES) class. New fish indices are developed for a defined geographical area, using specific sampling method and under locally relevant pressure fields. The former two factors, area and sampling methods, define the relevant reference condition in the calculation of Ecological Quality Ratios (EQR) and the latter factor, human pressures, define the índex structure and especially the fish metric selection. To assess index relevance across areas, we calculated a suite of transitional fish indices on a standardized WISER dataset and then compared the agreement of the outcomes (using correlation analysis). The application of current indices to areas (or countries) different from the area in which it was originally developed leads to inconclusive or spurious results. The failure to accommodate the diferente indices to a standardized dataset in this work clearly demonstrates the fundamental reliance of current fish indices on the sampling methods and design of monitoring programmes used in the development of the index. Despite this, for some indices, correlations although weaker are statistically significant, also indicating the possible agreement in successful intercalibration between these indices. Harmonization of BQE fish methodologies across Europe (common metrics) is unlikely by adapting or creating new fish indices but inter-comparison assessments are possible and valid using a common pressure index to harmonise diferente indices on a common scale. We found a negative response of fish quality features to pressure gradients which make BQE fish in TW suitable for greater ecological integration than other BQEs. However, successful assessment of Ecological Status (ES) require a matching combination of fish index, reference values and local dataset gathered with compatible sampling methods. Whole indices provide more consistent overall ES assessments but fish metrics considered individually may be more useful as a means to focus restoration measures. Future work is needed to identify those specific pressures affecting fish assemblages providing targets for minimising the effects of stress in mitigation and restoration plans. In order to achieve this, and although the interpretation of outcomes is still difficult, more recent transitional fish indices are leading in the use of comprehensive appraisal and validation exercises to test the responsiveness of BQEs for the assessment of ES. Here we proposed for the first time a simple sensitivity exercise under realistic scenarios of metric change to explore the expected inertia (i.e. the tendency to buffer ES change after quality alterations), dynamic range (i.e. the ratio between the largest and smallest possible ES values) and most relevant metric components (i.e. the those driving the most likely scenarios leading to ES change) from a multi-metric fish índex under relevant human pressure gradients. Overall, the behaviour of multi-metric índices under manipulations of metric scores clearly indicated that metric type, number of metrics used and correlations between metrics are important in determining the index performance, with indices including more and/or uncorrelated metrics or metrics with skewed distribution being less affected by extreme metric manipulations. Results of this analysis may be used to set realistic management targets and also to identify the aspects of the indices that are more likely to affect the outcomes leading to more robust and responsive indices. Further improvements of fish indices may be attained by reducing the variability confounding biological quality metrics. This variability is undesirable noise in assessments and can be technical (i.e. linked to the method of assessment including sampling effort) or natural (physicochemical and biological). The implication for assessments is that different facts might then confound the metric-pressure correlation (the ‘signal’ in the signal-to-noise ratio in the assessments) increasing uncertainty in ES assignment. Models showed that salinity class, depth, season, time of fishing (day vs. night) and year of fishing may influence the values of the fish metrics. The modelling exercise also demonstrated that unexplained variance remains generally much higher within-systems than between-systems suggesting a higher importance of sources of variability acting at the WB level. Modelling and improved standardization in monitoring campaigns should reduce uncertainty in ES assignment. One important factor that was assessed further was the effect of sampling effort. The results suggest that richness-based metrics require larger sampling efforts although a similar effortrelated bias may be an issue for density-based metrics if fish distribution is very patchy (i.e. schooling fish or those aggregated in specific habitats) and insufficient replicates are taken to fully characterise the patchiness in their distribution. It is apparent that to overcome a potential large source of error, the Reference Conditions must be defined according to the level of effort used in the monitoring programme or, conversely, the monitoring must be carried out at the same level of effort used to derive the Reference Condition. The WP finally explored the use of a predictive linear modelling approach to define reference conditions for fish metrics in transitional waters. The fish response data was modelled together with Corine Land Cover (CLC)-derived pressure proxies (% agricultural, urban and natural land coverage). Based on the obtained models, the expected metric score was predicted by setting pressure levels either to the lowest observed pressure in the dataset or to zero in order to define the sample and theoretical reference condition, respectively. Even when significant, the effect of pressures on fish metrics was generally very weak, probably reflecting the use of too-generic pressure indicators (such as land cover data instead of more relevant estuarine proxies such as dredging, port development, waterborne pollutants, etc). The best explanatory models included sampling factors and natural characteristics considered important discriminant features in the definition of water body types. In particular, the present work argues for considering not only estuaries and lagoons as different typologies but also other natural and design characteristic such as the gear type, the sampling season and the salinity class. Furthermore, a relevant reference needs to account for survey design bias, including rare species contribution to assessment datasets, patchiness, choice of pressure proxies or sampling gear. The modelling approach of fish metrics against the physicochemical variables has proved useful to derive Reference Conditions. This is important for the computation of relevant EQRs in Europe where there is a general lack of pristine areas or historical data on fish BQE and it provides an alternative to best professional judgment. Taking all WP analysis and case studies together, the work conducted has highlighted the following key messages and linked research needs necessary to optimize BQE fish for the quality assessment of transitional waters: Key Message 01: Harmonization of BQE fish methodologies across Europe (common metrics) is unlikely by adapting or creating new fish indices but inter-comparison assessments are possible and valid using a common pressure index to harmonise diferente indices on a common scale. Research needs to be focused on more widely-applicable fish indices will require the formulation of completely new indices based on a more flexible use of fish metrics according to system typologies, relevance and, probably, an increased use of functional traits. For current indices, further research on a method of intercalibration is needed. Key Message 02: BQE Fish in TW respond consistently to human pressure gradients across transitional waters providing the means to assess Ecological Status (ES). Further work will be needed to identify those specific pressures affecting fish assemblages providing targets for minimising the effects of stress in mitigation and restoration plans. Key Message 03 Although the interpretation of outcomes is still difficult, more recente transitional fish indices are leading in the use of comprehensive appraisal and validation exercises to test the performance of BQEs in the assessment of Ecological Status (ES). Further appraisal of fish indices behaviour is needed to understand the meaning of the quality outcomes, to set realistic management targets and also to identify the aspects of the índices that are more likely to affect the outcomes leading to more robust and responsive indices Key Message 04 Uncertainty levels associated with metric variability in multi-metric fish indices can be managed to increase the confidence in Ecological Status (ES) class assignment. Further research is needed to include knowledge of habitat partition within systems, to understand metrics behaviour and precision, to test new combination rules allowing metric weighting by robustness and importantly to evaluate more robust sampling tools and methods. Key Message 05 Reference conditions for BQE fish-based quality assessments can be objectively estimated using predictive modelling. Further refinements will require the use of better pressure proxies, robust metrics amenable to modelling and to account for survey design bias (effort & choice of sampling gear) at the relevant scales used in monitoring programmes.info:eu-repo/semantics/publishedVersio

Senile Cardiac Amyloidosis: An Undervalued Cause of Heart Failure.

Despite recurrent hospitalizations for heart failure exacerbations, the underlying cause can be missed. Senile amyloidosis is a disease prevalent in the elderly African American population. Senile amyloidosis is underdiagnosed as a cause of heart failure because of its occurrence with more common comorbidities, such as long-standing systemic hypertension. It is important to maintain a high index of suspicion for senile amyloidosis in patients such as this case, who presented with multiple exacerbations of heart failure combined with characteristic electrocardiographic and echocardiographic findings

Pairing fluctuations and pseudogaps in the attractive Hubbard model

The two-dimensional attractive Hubbard model is studied in the weak to intermediate coupling regime by employing a non-perturbative approach. It is first shown that this approach is in quantitative agreement with Monte Carlo calculations for both single-particle and two-particle quantities. Both the density of states and the single-particle spectral weight show a pseudogap at the Fermi energy below some characteristic temperature T*, also in good agreement with quantum Monte Carlo calculations. The pseudogap is caused by critical pairing fluctuations in the low-temperature renormalized classical regime $\omega < T$ of the two-dimensional system. With increasing temperature the spectral weight fills in the pseudogap instead of closing it and the pseudogap appears earlier in the density of states than in the spectral function. Small temperature changes around T* can modify the spectral weight over frequency scales much larger than temperature. Several qualitative results for the s-wave case should remain true for d-wave superconductors.Comment: 20 pages, 12 figure

The bZIP transcription factor SPA Heterodimerizing Protein represses glutenin synthesis in Triticum aestivum

The quality of wheat grain is mainly determined by the quantity and composition of its grain storage proteins (GSPs). Grain storage proteins consist of low- and high-molecular-weight glutenins (LMW-GS and HMW-GS, respectively) and gliadins. The synthesis of these proteins is essentially regulated at the transcriptional level and by the availability of nitrogen and sulfur. The regulation network has been extensively studied in barley where BLZ1 and BLZ2, members of the basic leucine zipper (bZIP) family, activate the synthesis of hordeins. To date, in wheat, only the ortholog of BLZ2, Storage Protein Activator (SPA), has been identified as playing a major role in the regulation of GSP synthesis. Here, the ortholog of BLZ1, named SPA Heterodimerizing Protein (SHP), was identified and its involvement in the transcriptional regulation of the genes coding for GSPs was analyzed. In gel mobility shift assays, SHP binds cis-motifs known to bind to bZIP family transcription factors in HMW-GS and LMW-GS promoters. Moreover, we showed by transient expression assays in wheat endosperm that SHP acts as a repressor of the activity of these gene promoters. This result was confirmed in transgenic lines overexpressing SHP, which were grown with low and high nitrogen supply. The phenotype of SHP-overexpressing lines showed a lower quantity of both LMW-GS and HMW-GS, while the quantity of gliadin was unchanged, whatever the nitrogen availability. Thus, the gliadin/glutenin ratio was increased, which suggests that gliadin and glutenin genes may be differently regulated