Effects of terlipressin as early treatment for protection of brain in a model of haemorrhagic shock

Introduction: We investigated whether treatment with terlipressin during recovery from hypotension due to haemorrhagic shock (HS) is effective in restoring cerebral perfusion pressure (CPP) and brain tissue markers of water balance, oxidative stress and apoptosis. Methods: In this randomised controlled study, animals undergoing HS (target mean arterial pressure (MAP) 40 mmHg for 30 minutes) were randomised to receive lactated Ringer’s solution (LR group; n =14; volume equal to three times the volume bled), terlipressin (TERLI group; n =14; 2-mg bolus), no treatment (HAEMO group; n =12) or sham (n =6). CPP, systemic haemodynamics (thermodilution technique) and blood gas analyses were registered at baseline, shock and 5, 30, 60 (T60), 90 and 120 minutes after treatment (T120). After the animals were killed, brain tissue samples were obtained to measure markers of water balance (aquaporin-4 (AQP4)), Na+-K+-2Cl− co-transporter (NKCC1)), oxidative stress (thiobarbituric acid reactive substances (TBARS) and manganese superoxide dismutase (MnSOD)) and apoptotic damage (Bcl-x and Bax). Results: Despite the HS-induced decrease in cardiac output (CO) and hyperlactataemia, resuscitation with terlipressin recovered MAP and resulted in restoration of CPP and in cerebral protection expressed by normalisation of AQP4, NKCC1, TBARS and MnSOD expression and Bcl-x/Bax ratio at T60 and T120 compared with sham animals. In the LR group, CO and blood lactate levels were recovered, but the CPP and MAP were significantly decreased and TBARS levels and AQP4, NKCC1 and MnSOD expression and Bcl-x/Bax ratio were significantly increased at T60 and T120 compared with the sham group. Conclusions: During recovery from HS-induced hypotension, terlipressin was effective in normalising CPP and cerebral markers of water balance, oxidative damage and apoptosis. The role of this pressor agent on brain perfusion in HS requires further investigation

Freshwater bivalve shells as hydrologic archives in the Congo Basin

We test the applicability of bivalve shell oxygen isotope composition to reconstruct hydrological dynamics in four riverine sites in the Congo River basin. Twenty-three specimens from the Unionoida order were collected from locations where long-term discharge data are available, and in situ measurements and water samples were collected over several years. Due to the highly variable (species-specific) shell morphology, various sampling techniques were used to analyze the shell sections; however, every specimen recorded the seasonality of the host water oxygen stable isotope composition (δ 18 O w ) in its δ 18 O shell record. Discharge data showed an inverse relationship with δ 18 O w values, which was well described with a logarithmic fit. An exception was the Kasai River, where the δ 18 O w record shows an additional peak occurring during the high discharge period, which renders the discharge-δ 18 O w relationship more complex than in the other systems investigated. Low ratios of maximum to minimum discharge (Q max /Q min ) were found to result in a low δ 18 O w amplitude, which was reflected as low δ 18 O shell variability. The Congo and Kasai rivers had Q max /Q min ratios ~2 to 2.5, while the Oubangui showed a much higher Q max /Q min (~19). Shells correspondingly showed a large δ 18 O shell range (amplitude between 2.4 and 5.0‰) for individual Oubangui shells, and lower amplitude for other sites (1.0 to 2.2‰). Thus, shells have a high resolving power to be used to record hydrological variability, since long-term changes in precipitation pattern, discharge, land-use change, or other hydrological changes have an influence on δ 18 O w values. Shells with wide range of δ 18 O values reflect high seasonal variability in rivers, while shells with lower δ 18O amplitude correspond to sites with more steady river conditions over the year. Our study illustrates that fossil shell δ 18 O values could indicate Q max /Q min values in ancient African river systems.AFRIVA

A prospective study of nutrition education and oral nutritional supplementation in patients with Alzheimer's disease

<p>Abstract</p> <p>Background</p> <p>Weight loss in patients with Alzheimer's disease (AD) is a common clinical manifestation that may have clinical significance.</p> <p>Objectives</p> <p>To evaluate if there is a difference between nutrition education and oral nutritional supplementation on nutritional status in patients with AD.</p> <p>Methods</p> <p>A randomized, prospective 6-month study which enrolled 90 subjects with probable AD aged 65 years or older divided into 3 groups: Control Group (CG) [n = 27], Education Group (EG) [n = 25], which participated in an education program and Supplementation Group (SG) [n = 26], which received two daily servings of oral nutritional supplementation. Subjects were assessed for anthropometric data (weight, height, BMI, TSF, AC and AMC), biochemical data (total protein, albumin, and total lymphocyte count), CDR (Clinical Dementia Rating), MMSE (Mini-mental state examination), as well as dependence during meals.</p> <p>Results</p> <p>The SG showed a significant improvement in the following anthropometric measurements: weight (H calc = 22.12, p =< 0.001), BMI (H calc = 22.12, p =< 0.001), AC (H calc = 12.99, p =< 0.002), and AMC (H calc = 8.67, p =< 0.013) compared to the CG and EG. BMI of the EG was significantly greater compared to the CG. There were significant changes in total protein (H calc = 6.17, p =< 0.046), and total lymphocyte count in the SG compared to the other groups (H cal = 7.94, p = 0.019).</p> <p>Conclusion</p> <p>Oral nutritional supplementation is more effective compared to nutrition education in improving nutritional status.</p

Glucose Availability and AMP-Activated Protein Kinase Link Energy Metabolism and Innate Immunity in the Bovine Endometrium

Defences against the bacteria that usually infect the endometrium of postpartum cattle are impaired when there is metabolic energy stress, leading to endometritis and infertility. The endometrial response to bacteria depends on innate immunity, with recognition of pathogen-associated molecular patterns stimulating inflammation, characterised by secretion of interleukin (IL)-1β, IL-6 and IL-8. How metabolic stress impacts tissue responses to pathogens is unclear, but integration of energy metabolism and innate immunity means that stressing one system might affect the other. Here we tested the hypothesis that homeostatic pathways integrate energy metabolism and innate immunity in bovine endometrial tissue. Glucose deprivation reduced the secretion of IL-1β, IL-6 and IL-8 from ex vivo organ cultures of bovine endometrium challenged with the pathogen-associated molecular patterns lipopolysaccharide and bacterial lipopeptide. Endometrial inflammatory responses to lipopolysaccharide were also reduced by small molecules that activate or inhibit the intracellular sensor of energy, AMP-activated protein kinase (AMPK). However, inhibition of mammalian target of rapamycin, which is a more global metabolic sensor than AMPK, had little effect on inflammation. Similarly, endometrial inflammatory responses to lipopolysaccharide were not affected by insulin-like growth factor-1, which is an endocrine regulator of metabolism. Interestingly, the inflammatory responses to lipopolysaccharide increased endometrial glucose consumption and induced the Warburg effect, which could exacerbate deficits in glucose availability in the tissue. In conclusion, metabolic energy stress perturbed inflammatory responses to pathogen-associated molecular patterns in bovine endometrial tissue, and the most fundamental regulators of cellular energy, glucose availability and AMPK, had the greatest impact on innate immunity

Employment and sociodemographic characteristics: a study of increasing precarity in the health districts of Belo Horizonte, Brazil

<p>Abstract</p> <p>Background</p> <p>The fundamental importance of human resources for the development of health care systems is recognized the world over. Health districts, which constitute the middle level of the municipal health care system in the city of Belo Horizonte, Brazil, deal with demands from all parts of the system. This research seeks to provide the essential features required in order to understand the phenomenon of increase in precarity of employment in these health districts.</p> <p>Methods</p> <p>The legal and human resource management documents used by the Municipal Health Secretariat of the City of Belo Horizonte were adopted as the corpus for this research. In order to analyse the changes in employment (2002–2006), the data were collected from ArteRH, a computerized database dealing specifically with data related to human resources, which began operating in 2001. The workers were classified into permanent and non-permanent groups, and their contractual rights were described. Employment dynamics and changes were examined, concentrating on the incorporation of workers and on their social and employment rights during the period under study. The comparative data for the two groups obtained were presented in frequency distribution tables according to type of employment, sex, age group, level of education and wages from 2002 to 2006.</p> <p>Results</p> <p>There was a clear difference between the permanent worker and non-permanent worker groups as regards existing guaranteed employment rights and social security. The increase in the number of non-permanent workers in the workforce, the growing proportion of older workers among the permanently employed and the real wage reductions during the period from 2002 to 2006 are indicative of the process of growing precarity of employment in the group studied.</p> <p>Conclusion</p> <p>It is a plausible supposition that the demand for health reforms, along with the legal limits imposed on financial expenditure, gave rise to the new types of contract and the present employment situation in the health districts in Belo Horizonte.</p

Fetal alleles predisposing to metabolically favourable adiposity are associated with higher birth weight

This is the final version. Available on open access from Oxford University Press via the DOI in this record Data Availability: Our study used both published summary results (i.e. taking results from published research papers and websites) and individual participant cohort data as follows: The data for the GWAS of BMI is available here. https://portals.broadinstitute.org/collaboration/giant/index.php/GIANT_consortium_data_files The data for the GWAS of body fat percentage is available here. https://walker05.u.hpc.mssm.edu The data for the GWAS of birth weight is available here. https://egg-consortium.org/birth-weight-2019.htm The references to those published data sources are provided in the main paper. We used individual participant data for the genetic association analyses from the UK Biobank, ALSPAC, BiB, EFSOCH and HAPO cohorts. The data in UK Biobank, ALSPAC and BiB are fully available, via managed systems, to any researchers. The managed system for both studies is a requirement of the study funders but access is not restricted on the basis of overlap with other applications to use the data or on the basis of peer review of the proposed science. UK Biobank. Full information on how to access these data can be found here - https://www.ukbiobank.ac.uk/using-the-resource/ ALSPAC. The ALSPAC data management plan (http://www.bristol.ac.uk/alspac/researchers/data-access/documents/alspac-data-managementplan.pdf ) describes in detail the policy regarding data sharing, which is through a system of managed open access. The steps below highlight how to apply for access to the data included in this paper and all other ALSPAC data. 27 1. Please read the ALSPAC access policy (PDF, 627kB) which describes the process of accessing the data and samples in detail, and outlines the costs associated with doing so. 2. You may also find it useful to browse the fully searchable ALSPAC research proposals database, which lists all research projects that have been approved since April 2011. 3. Please submit your research proposal for consideration by the ALSPAC Executive Committee. You will receive a response within 10 working days to advise you whether your proposal has been approved. If you have any questions about accessing data, please email [email protected]. BiB. Full information on how to access these data can be found here - https://borninbradford.nhs.uk/research/how-to-access-data/ HAPO. For access to the data used in this study, please contact Dr. Rachel Freathy ([email protected]) and Prof. William Lowe Jr ([email protected]). The website describing the study and other data available is https://www.ncbi.nlm.nih.gov/projects/gap/cgibin/study.cgi?study_id=phs000096.v4.p1 If you have further questions, please email Dr William Lowe at [email protected] EFSOCH. Requests for access to the original EFSOCH dataset should be made in writing in the first instance to the EFSOCH data team via the Exeter Clinical Research Facility [email protected]: Higher birthweight is associated with higher adult BMI. Alleles that predispose to greater adult adiposity might act in fetal life to increase fetal growth and birthweight. Whether there are fetal effects of recently identified adult metabolically favourable adiposity alleles on birthweight is unknown. Aim We aimed to test the effect on birthweight of fetal genetic predisposition to higher metabolically favourable adult adiposity and compare that with the effect of fetal genetic predisposition to higher adult BMI. METHODS: We used published GWAS data (n = upto 406 063) to estimate fetal effects on birthweight (adjusting for maternal genotype) of alleles known to raise metabolically favourable adult adiposity or BMI. We combined summary data across SNPs with random effects meta-analyses. We performed weighted linear regression of SNP-birthweight effects against SNP-adult adiposity effects to test for a dose-dependent association. RESULTS: Fetal genetic predisposition to higher metabolically favourable adult adiposity and higher adult BMI were both associated with higher birthweight (3grams per effect allele (95%CI, 1 to 5) averaged over 14 SNPs; p = 0.002; 0.5grams per effect allele (95%CI, 0 to 1) averaged over 76 SNPs; p = 0.042, respectively). SNPs with greater effects on metabolically favourable adiposity tended to have greater effects on birthweight (R2 = 0.2912, p = 0.027). There was no dose-dependent association for BMI (R2 = -0.0019, p = 0.602). CONCLUSIONS: Fetal genetic predisposition to both higher adult metabolically favourable adiposity and BMI is associated with birthweight. Fetal effects of metabolically favourable adiposity-raising alleles on birthweight are modestly proportional to their effects on future adiposity, but those of BMI-raising alleles are not.US National Institute of HealthEuropean Research Council (ERC)British Heart Foundatio