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BackgroundPoor medication adherence is a major challenge in asthma, and objective assessment of inhaler adherence is needed. The InspirerMundi app aims to monitor adherence while providing a positive experience through gamification and social support. ObjectiveThis study aimed to evaluate the feasibility and acceptability of the InspirerMundi app to monitor medication adherence in adolescents and adults with persistent asthma (treated with daily inhaled medication). MethodsA 1-month mixed method multicenter observational study was conducted in 26 secondary care centers from Portugal and Spain. During an initial face-to-face visit, physicians reported patients’ asthma therapeutic plan in a structured questionnaire. During the visits, patients were invited to use the app daily to register their asthma medication intakes. A scheduled intake was considered taken when patients registered the intake (inhaler, blister, or other drug formulation) by using the image-based medication detection tool. At 1 month, patients were interviewed by phone, and app satisfaction was assessed on a 1 (low) to 5 (high) scale. Patients were also asked to point out the most and least preferred app features and make suggestions for future app improvements. ResultsA total of 107 patients (median 27 [P25-P75 14-40] years) were invited, 92.5% (99/107) installed the app, and 73.8% (79/107) completed the 1-month interview. Patients interacted with the app a median of 9 (P25-P75 1-24) days. At least one medication was registered in the app by 78% (77/99) of patients. A total of 53% (52/99) of participants registered all prescribed inhalers, and 34% (34/99) registered the complete asthma therapeutic plan. Median medication adherence was 75% (P25-P75 25%-90%) for inhalers and 82% (P25-P75 50%-94%) for other drug formulations. Patients were globally satisfied with the app, with 75% (59/79) scoring ≥4,; adherence monitoring, symptom monitoring, and gamification features being the most highly scored components; and the medication detection tool among the lowest scored. A total of 53% (42/79) of the patients stated that the app had motivated them to improve adherence to inhaled medication and 77% (61/79) would recommend the app to other patients. Patient feedback was reflected in 4 major themes: medication-related features (67/79, 85%), gamification and social network (33/79, 42%), symptom monitoring and physician communication (21/79, 27%), and other aspects (16/79, 20%). ConclusionsThe InspirerMundi app was feasible and acceptable to monitor medication adherence in patients with asthma. Based on patient feedback and to increase the registering of medications, the therapeutic plan registration and medication detection tool were redesigned. Our results highlight the importance of patient participation to produce a patient-centered and engaging mHealth asthma app.

New additional conditions required for the uniqueness of the 2D elastostatic problems formulated in terms of potential functions for the derived Papkovich-Neuber representations, are studied. Two cases are considered, each of them formulated by the scalar potential function plus one of the rectangular non-zero components of the vector potential function. For these formulations, in addition to the original (physical) boundary conditions, two new additional conditions are required. In addition, for the complete Papkovich-Neuber formulation, expressed by the scalar potential plus two components of the vector potential, the additional conditions established previously for the three-dimensional case in z-convex domain can be applied. To show the usefulness of these new conditions in a numerical scheme two applications are numerically solved by the network method for the three cases of potential formulations.

In this paper, some classification methods are applied to a set of texts with the aim of studying the probability that the book Novela de la tía fingida has been written by Miguel de Cervantes. This novel has been historically attributed to him but there are some encountered positions about this. The methods used in this paper range from: logistic regression, additive logistic regression, linear, quadratic, regularized, mixture and flexible discriminant analysis, classification tree, k-nearest neighbour, Naive Bayes method and support vector machines. Methods were trained and applied using a corpus of authors contemporary to Cervantes as Lope de Vega, Jerónimo de Pasamonte, Alonso Fernández de Avellaneda, Mateo Alemán, and Francisco de Quevedo and more than forty variables, mainly words and punctuation marks, measured over written texts by these authors. Respect to these methods, most of them classify the novel as another Cervantes’ work; however, is our recommendation to include more texts from these authors and more authors.En este artículo se aplican algunos métodos de clasificación a un conjunto de textos con el objetivo de estudiar la probabilidad que el libro Novela de la tía fingida haya sido escrita por Miguel de Cervantes. Esta novela se le ha atribuido históricamente, pero existen algunas posiciones encontradas al respecto. Los métodos usados en este artículo contemplan: regresión logística, regresión logística aditiva, análisis discriminante lineal, cuadrático, regularizado, de mezclas y flexible, árboles de clasificación, método de los k-ésimos vecinos más cercanos, método de Bayes ingenuo y máquinas de soporte vectorial. Los métodos fueron calibrados y aplicados utilizando un corpus de autores contemporáneos a Cervantes (Lope de Vega, Jerónimo de Pasamonte, Alonso Fernández de Avellaneda, Mateo Alemán y Francisco de Quevedo) junto con más de cuarenta variables, principalmente palabras y signos de puntuación, medidas sobre muestras de los textos escritos por estos autores. Con respecto a estos métodos, la mayoría clasifica la obra como cervantina; sin embargo, es recomendable ampliar el corpus utilizado para el estudio e incluir más autores para la comparación.

In this paperwe give new existence results for complete non-orientable minimal surfaces in ℝ3 with prescribed topology and asymptotic behavior

The aim of this research was to propose a solution which applies the Crowdsourcing concept as the use of Information Technology to determine the perception of a social environment, which can perform a raised topic by an entity. In this case, the perception of Ruben Cruz Velez hospital with respect to: What opinion would you give about the Hospital Prevention and Promotion program?, in order to evaluate throughout Crowdsourcing, the Monitoring and Control Inspection (IVC) mechanisms for the provision of health services and component effectiveness, processes and standards of the Mandatory Quality Assurance System and their impact on provision of health services to users in an accessible and equitable manner.It is important to highlight that the development of a web platform that allows citizen participation to evaluate the mechanisms of Inspection of Monitoring and Control (IVC) of the provision of health services, analyzing the effectiveness of corrective actions and their impact on The provision of services to users in an accessible and equitable manner. Undoubtedly, in order to understand the current development and situation of traditional medicine in diverse geographical and cultural contexts, the way it adapts to its environment, and the type of health care available, it is necessary to locate it in the context of the models Health care in which it is inserted. The analysis of the current situation of traditional health systems, seen as subsystems of the total system, serves as a starting point for a more detailed reflection of their dynamics in Colombia, so thanks to the development of the CROWDSOURCING methodology as a tool To understand the current situation will help us to make valuable decisions for the future of the health sector particularly the beneficiary entities.

Abstract Background Subtelomeric multigene families of malaria parasites encode virulent determinants. The published genome sequence of Plasmodium vivax revealed the largest subtelomeric multigene family of human malaria parasites, the vir super-family, presently composed of 346 vir genes subdivided into 12 different subfamilies based on sequence homologies detected by BLAST. Results A novel computational approach was used to redefine vir genes. First, a protein-weighted graph was built based on BLAST alignments. This graph was processed to ensure that edge weights are not exclusively based on the BLAST score between the two corresponding proteins, but strongly dependant on their graph neighbours and their associations. Then the Markov Clustering Algorithm was applied to the protein graph. Next, the Homology Block concept was used to further validate this clustering approach. Finally, proteome-wide analysis was carried out to predict new VIR members. Results showed that (i) three previous subfamilies cannot longer be classified as vir genes; (ii) most previously unclustered vir genes were clustered into vir subfamilies; (iii) 39 hypothetical proteins were predicted as VIR proteins; (iv) many of these findings are supported by a number of structural and functional evidences, sub-cellular localization studies, gene expression analysis and chromosome localization (v) this approach can be used to study other multigene families in malaria. Conclusions This methodology, resource and new classification of vir genes will contribute to a new structural framing of this multigene family and other multigene families of malaria parasites, facilitating the design of experiments to understand their role in pathology, which in turn may help furthering vaccine development.

Abstract Background Regulatory motifs describe sets of related transcription factor binding sites (TFBSs) and can be represented as position frequency matrices (PFMs). De novo identification of TFBSs is a crucial problem in computational biology which includes the issue of comparing putative motifs with one another and with motifs that are already known. The relative importance of each nucleotide within a given position in the PFMs should be considered in order to compute PFM similarities. Furthermore, biological data are inherently noisy and imprecise. Fuzzy set theory is particularly suitable for modeling imprecise data, whereas fuzzy integrals are highly appropriate for representing the interaction among different information sources. Results We propose FISim, a new similarity measure between PFMs, based on the fuzzy integral of the distance of the nucleotides with respect to the information content of the positions. Unlike existing methods, FISim is designed to consider the higher contribution of better conserved positions to the binding affinity. FISim provides excellent results when dealing with sets of randomly generated motifs, and outperforms the remaining methods when handling real datasets of related motifs. Furthermore, we propose a new cluster methodology based on kernel theory together with FISim to obtain groups of related motifs potentially bound by the same TFs, providing more robust results than existing approaches. Conclusion FISim corrects a design flaw of the most popular methods, whose measures favour similarity of low information content positions. We use our measure to successfully identify motifs that describe binding sites for the same TF and to solve real-life problems. In this study the reliability of fuzzy technology for motif comparison tasks is proven.

Abstract Background Last years' mapping of diverse genomes has generated huge amounts of biological data which are currently dispersed through many databases. Integration of the information available in the various databases is required to unveil possible associations relating already known data. Biological data are often imprecise and noisy. Fuzzy set theory is specially suitable to model imprecise data while association rules are very appropriate to integrate heterogeneous data. Results In this work we propose a novel fuzzy methodology based on a fuzzy association rule mining method for biological knowledge extraction. We apply this methodology over a yeast genome dataset containing heterogeneous information regarding structural and functional genome features. A number of association rules have been found, many of them agreeing with previous research in the area. In addition, a comparison between crisp and fuzzy results proves the fuzzy associations to be more reliable than crisp ones. Conclusion An integrative approach as the one carried out in this work can unveil significant knowledge which is currently hidden and dispersed through the existing biological databases. It is shown that fuzzy association rules can model this knowledge in an intuitive way by using linguistic labels and few easy-understandable parameters.

Background: R21 is a novel malaria vaccine, composed of a fusion protein of the malaria circumsporozoite protein and hepatitis B surface antigen. Following favourable safety and immunogenicity in a phase 1 study, we aimed to assess the efficacy of R21 administered with Matrix-M (R21/MM) against clinical malaria in adults from the UK who were malaria naive in a controlled human malaria infection study., Methods: In this open-label, partially blinded, phase 1-2A controlled human malaria infection study undertaken in Oxford, Southampton, and London, UK, we tested five novel vaccination regimens of R21/MM. A standard three-dose regimen (groups 1 and 6) was compared with a reduced (fractional) third dose (groups 2 and 5) of R21/MM, concomitant administration with viral vectors ChAd63-MVA expressing ME-TRAP (group 3), and a two-dose R21/MM regimen (group 7). Controlled Human Malaria Infection (CHMI) was delivered by mosquito bite at Imperial College London, London, UK, 3-4 weeks after final vaccination (or 18 months after final vaccination for group 6) alongside unvaccinated controls (groups 4A and 4B). The primary outcome measures were to assess safety of the vaccines in healthy malaria-naive volunteers and the efficacy (occurrence of blood-stage malaria infection) of the different vaccine regimens compared with non-vaccinated controls after CHMI. The trial was registered with ClinicalTrials.gov (NCT02905019)., Findings: 66 volunteers were enrolled with 59 undergoing subsequent CHMI. All vaccination schedules were well tolerated. The highest level of protection against CHMI was observed in participants receiving the standard three-dose regimen of R21/MM (group 1, nine of 11 volunteers protected) with protection maintained in three of five volunteers re-challenged by CHMI 7·5 months later. Protection against malaria was also seen in group 2, group 3, and group 5 compared with unvaccinated control participants. Total IgG antibody responses to the NANP repeat region of circumsporozoite protein peaked after the third dose of R21/MM in all volunteers and were well maintained to 90 days after challenge. Reducing the third dose did not affect protection or antibody concentrations., Interpretation: Our study shows that R21/MM elicits high-level efficacy against clinical malaria in a controlled human infection model of malaria in adults who are malaria naive. These data supported the evaluation of R21/MM in field efficacy trials in the target population of young children in malaria-endemic areas., Funding: EU Horizon 2020, the UK Medical Research Council, the European Commission, the UK National Institute of Health Research, the Imperial NIHR Clinical Research Facility, the Oxford NIHR Biomedical Research Centre, and the Wellcome Trust., Competing Interests: Declaration of interests KAC, NV, KJE, and AVSH are named as co-inventors or contributors on patent filings related to the R21 vaccine candidate. KJE was an employee of the University of Oxford, Oxford, UK at the time of the work and is now an employee of GSK. KJE holds restricted shares in the GSK group of companies. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The R21/Matrix-M vaccine has demonstrated high efficacy against Plasmodium falciparum clinical malaria in children in sub-Saharan Africa. Using trial data, we aimed to estimate the public health impact and cost-effectiveness of vaccine introduction across sub-Saharan Africa., Methods: We fitted a semi-mechanistic model of the relationship between anti-circumsporozoite protein antibody titres and vaccine efficacy to data from 3 years of follow-up in the phase 2b trial of R21/Matrix-M in Nanoro, Burkina Faso. We validated the model by comparing predicted vaccine efficacy to that observed over 12-18 months in the phase 3 trial. Integrating this framework within a mathematical transmission model, we estimated the cases, malaria deaths, and disability-adjusted life-years (DALYs) averted and cost-effectiveness over a 15-year time horizon across a range of transmission settings in sub-Saharan Africa. Cost-effectiveness was estimated incorporating the cost of vaccine introduction (dose, consumables, and delivery) relative to existing interventions at baseline. We report estimates at a median of 20% parasite prevalence in children aged 2-10 years (PfPR 2-10 ) and ranges from 3% to 65% PfPR 2-10 ., Findings: Anti-circumsporozoite protein antibody titres were found to satisfy the criteria for a surrogate of protection for vaccine efficacy against clinical malaria. Age-based implementation of a four-dose regimen of R21/Matrix-M vaccine was estimated to avert 181 825 (range 38 815-333 491) clinical cases per 100 000 fully vaccinated children in perennial settings and 202 017 (29 868-405 702) clinical cases per 100 000 fully vaccinated children in seasonal settings. Similar estimates were obtained for seasonal or hybrid implementation. Under an assumed vaccine dose price of US$3, the incremental cost per clinical case averted was $7 (range 4-48) in perennial settings and $6 (3-63) in seasonal settings and the incremental cost per DALY averted was $34 (29-139) in perennial settings and $30 (22-172) in seasonal settings, with lower cost-effectiveness ratios in settings with higher PfPR 2-10 ., Interpretation: Introduction of the R21/Matrix-M malaria vaccine could have a substantial public health benefit across sub-Saharan Africa., Funding: The Wellcome Trust, the Bill & Melinda Gates Foundation, the UK Medical Research Council, the European and Developing Countries Clinical Trials Partnership 2 and 3, the NIHR Oxford Biomedical Research Centre, and the Serum Institute of India, Open Philanthropy., Competing Interests: Declaration of interests AVSH and KJE are named as co-inventors on patent applications related to R21 and are entitled to a royalty share on any future income in conformity with the University of Oxford's policy. KJE was an employee of the University of Oxford at the time of the work and is now an employee of GSK. KJE holds restricted shares in the GSK group of companies. The University of Oxford has received funding from the Serum Institute of India to support funding of several African trials including the ongoing phase 3 trial of R21/Matrix-M. AVSH is chief investigator of these trials. PW has received funding from Gavi and the Wellcome Trust in the past 36 months. ACG has received funding from Gavi and NIH and consulting fees from the Global Fund in the past 36 months and is a trustee at Malaria No More UK. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

N-butylbenzenesulfonamide (NBBS) is a high-production volume plasticizer that is an emerging contaminant of concern for environmental and human health. To understand the risks and health effects of exposure to NBBS, studies were conducted in adult-exposed mice and developmentally exposed rats to evaluate the potential for NBBS to modulate the immune system. Beginning between 8 and 9 weeks of age, dosed feed containing NBBS at concentrations of 0, 313, 625, 1250, 2500, and 5000 ppm was continuously provided to B6C3F1/N female mice for 28 days. Dosed feed was also continuously provided to time-mated Harlan Sprague Dawley (Sprague Dawley SD) rats at concentrations of 0-, 250-, 500-, and 1000-ppm NBBS from gestation day 6 to postnatal day 28 and in F1 rats until 11-14 weeks of age. Functional assessments of innate, humoral, and cell-mediated immunity were conducted in adult female mice and F1 rats following exposure to NBBS. In female mice, NBBS treatment suppressed the antibody-forming cell (AFC) response to SRBC with small increases in T-cell responses and natural killer (NK)-cell activity. In developmentally exposed rats, NBBS treatment-related immune effects were sex dependent. A positive trend in NK-cell activity occurred in male F1 rats while a negative trend occurred in female F1 rats. The AFC response to SRBC was decreased in female F1 rats but not in male F1 rats. These data provide evidence that oral exposure to NBBS has the potential to produce immunomodulatory effects on both innate and adaptive immune responses, and these effects appear to have some dependence on species, sex, and period of exposure (developmental vs adult)., (Published by Oxford University Press on behalf of the Society of Toxicology 2023.)

Chikungunya virus (CHIKV) is a reemerging mosquito-borne virus that causes swift outbreaks. Major concerns are the persistent and disabling polyarthralgia in infected individuals. Here we present the results from a first-in-human trial of the candidate simian adenovirus vectored vaccine ChAdOx1 Chik, expressing the CHIKV full-length structural polyprotein (Capsid, E3, E2, 6k and E1). 24 adult healthy volunteers aged 18-50 years, were recruited in a dose escalation, open-label, nonrandomized and uncontrolled phase 1 trial (registry NCT03590392). Participants received a single intramuscular injection of ChAdOx1 Chik at one of the three preestablished dosages and were followed-up for 6 months. The primary objective was to assess safety and tolerability of ChAdOx1 Chik. The secondary objective was to assess the humoral and cellular immunogenicity. ChAdOx1 Chik was safe at all doses tested with no serious adverse reactions reported. The vast majority of solicited adverse events were mild or moderate, and self-limiting in nature. A single dose induced IgG and T-cell responses against the CHIKV structural antigens. Broadly neutralizing antibodies against the four CHIKV lineages were found in all participants and as early as 2 weeks after vaccination. In summary, ChAdOx1 Chik showed excellent safety, tolerability and 100% PRNT 50 seroconversion after a single dose., (© 2021. The Author(s).)

Background: Cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection continue to rise in the Arabian Peninsula 7 years after it was first described in Saudi Arabia. MERS-CoV poses a significant risk to public health security because of an absence of currently available effective countermeasures. We aimed to assess the safety and immunogenicity of the candidate simian adenovirus-vectored vaccine expressing the full-length spike surface glycoprotein, ChAdOx1 MERS, in humans., Methods: This dose-escalation, open-label, non-randomised, uncontrolled, phase 1 trial was done at the Centre for Clinical Vaccinology and Tropical Medicine (Oxford, UK) and included healthy people aged 18-50 years with negative pre-vaccination tests for HIV antibodies, hepatitis B surface antigen, and hepatitis C antibodies (and a negative urinary pregnancy test for women). Participants received a single intramuscular injection of ChAdOx1 MERS at three different doses: the low-dose group received 5 × 10 9 viral particles, the intermediate-dose group received 2·5 × 10 10 viral particles, and the high-dose group received 5 × 10 10 viral particles. The primary objective was to assess safety and tolerability of ChAdOx1 MERS, measured by the occurrence of solicited, unsolicited, and serious adverse events after vaccination. The secondary objective was to assess the cellular and humoral immunogenicity of ChAdOx1 MERS, measured by interferon-γ-linked enzyme-linked immunospot, ELISA, and virus neutralising assays after vaccination. Participants were followed up for up to 12 months. This study is registered with ClinicalTrials.gov, NCT03399578., Findings: Between March 14 and Aug 15, 2018, 24 participants were enrolled: six were assigned to the low-dose group, nine to the intermediate-dose group, and nine to the high-dose group. All participants were available for follow-up at 6 months, but five (one in the low-dose group, one in the intermediate-dose group, and three in the high-dose group) were lost to follow-up at 12 months. A single dose of ChAdOx1 MERS was safe at doses up to 5 × 10 10 viral particles with no vaccine-related serious adverse events reported by 12 months. One serious adverse event reported was deemed to be not related to ChAdOx1 MERS. 92 (74% [95% CI 66-81]) of 124 solicited adverse events were mild, 31 (25% [18-33]) were moderate, and all were self-limiting. Unsolicited adverse events in the 28 days following vaccination considered to be possibly, probably, or definitely related to ChAdOx1 MERS were predominantly mild in nature and resolved within the follow-up period of 12 months. The proportion of moderate and severe adverse events was significantly higher in the high-dose group than in the intermediate-dose group (relative risk 5·83 [95% CI 2·11-17·42], p<0·0001) Laboratory adverse events considered to be at least possibly related to the study intervention were self-limiting and predominantly mild in severity. A significant increase from baseline in T-cell (p<0·003) and IgG (p<0·0001) responses to the MERS-CoV spike antigen was observed at all doses. Neutralising antibodies against live MERS-CoV were observed in four (44% [95% CI 19-73]) of nine participants in the high-dose group 28 days after vaccination, and 19 (79% [58-93]) of 24 participants had antibodies capable of neutralisation in a pseudotyped virus neutralisation assay., Interpretation: ChAdOx1 MERS was safe and well tolerated at all tested doses. A single dose was able to elicit both humoral and cellular responses against MERS-CoV. The results of this first-in-human clinical trial support clinical development progression into field phase 1b and 2 trials., Funding: UK Department of Health and Social Care, using UK Aid funding, managed by the UK National Institute for Health Research., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Loss-of-function mutations in the copper (Cu) transporter ATP7A cause Menkes disease. Menkes is an infantile, fatal, hereditary copper-deficiency disorder that is characterized by progressive neurological injury culminating in death, typically by 3 years of age. Severe copper deficiency leads to multiple pathologies, including impaired energy generation caused by cytochrome c oxidase dysfunction in the mitochondria. Here we report that the small molecule elesclomol escorted copper to the mitochondria and increased cytochrome c oxidase levels in the brain. Through this mechanism, elesclomol prevented detrimental neurodegenerative changes and improved the survival of the mottled-brindled mouse-a murine model of severe Menkes disease. Thus, elesclomol holds promise for the treatment of Menkes and associated disorders of hereditary copper deficiency., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Objective: Systematic review and meta-analysis to assess the effects of uterine or paracervical lidocaine application on pain control during IUD insertion., Methods: PubMed and five other electronic research databases were searched through 15 November 2017 for RCTs comparing lidocaine treatment vs. a control (placebo or no-intervention) to prevent pain during IUD insertion. Searched terms included 'IUD insertion', 'lidocaine' and 'randomised controlled trial'. RCTs evaluating lidocaine treatment before IUD insertion without restriction of language, age and IUD type. Pain measured by visual pain scales at tenaculum placement, IUD insertion and immediate post-IUD insertion. Results of random effects meta-analyses were reported as mean differences (MDs) of visual pain scale (VPS) scores and their 95% confidence intervals (CIs)., Results: Eleven RCTs (n = 1458 women) reporting paracervical lidocaine block or uterine mucosa lidocaine application before IUD insertion. Lidocaine produced lower VPS scores during tenaculum placement (MD -0.99, 95% CI: -1.73 to -0.26), IUD insertion (MD -1.26, 95% CI: -2.23 to -0.29) and immediate post-IUD insertion period (MD -1.25, 95% CI: -2.17 to -0.33)., Conclusion: Lidocaine treatment was associated with modest reduction of pain during tenaculum placement and after IUD insertion.

The flow of transgenes into landraces and wild relatives is an important biosafety concern. The case of transgene flow into local maize varieties in Mexico (the center of origin of maize) has been intensively debated over the past 15 years, including legal, political, and environmental disputes fanned by the existence of a significant scientific controversy over the methods used for the detection of transgenes. The use of diverse approaches and a lack of harmonized methods specific to the detection and monitoring of transgenes in landraces have generated both positive and negative results regarding contamination of Mexican maize with genetically modified material over the years. In this paper, we revisit the case of transgene contamination in Mexican maize and present a novel research approach based on socio-biological analysis of contrasting communities and seed management systems. Two communities were used to investigate how different social and biological factors can affect transgene flow and impact transgene spread in Mexico. Our results show the presence of transgenes in one community and thus support the position that transgenes are highly likely to be present in Mexican maize landraces. However, our work also demonstrates that the extent and frequency with which transgenes can be found will significantly depend on the societal characteristics and seed management systems of the local communities. Therefore, we argue that future analysis of transgene presence should include social research on the seed management practices in the sampling area so that more robust and comprehensive understandings and conclusions can be drawn.

Background: Obesity, insulin resistance and type 2 diabetes mellitus (T2DM) have been associated with endometrial cancer (EC). In this systematic review and meta-analysis we evaluated the effect of metformin on clinical outcomes in patients with EC and insulin resistance or T2DM., Methods: Four research databases were searched for original articles published in all languages up to 30 October 2016. Outcomes of interest were overall mortality (OM), cancer-specific mortality, disease progression, and metastases. We performed a random effect meta-analysis of adjusted effects expressed as hazard ratios (HR); heterogeneity among studies was described with the I 2 statistic., Results: Of the 290 retrieved citations, 6 retrospective cohort studies in women with EC (n=4723) met the inclusion criteria, and 8.9% to 23.8% were treated with metformin; OM data was available from 5 studies. In 4 studies of EC patients (n=4132), metformin use was associated with a significant reduction in OM in comparison with not using metformin (adjusted HR [aHR] 0.64, 95% CI 0.45-0.89, p=0.009). In three studies evaluating patients with EC and T2DM (n=2637), metformin use was associated with a significant reduction in OM (aHR 0.50, 95%CI 0.34-0.74, p=0.0006). There was low to moderate heterogeneity of adjusted effects across studies. There was no information about the effect of metformin on cancer-specific mortality, disease progression, or metastases., Conclusions: Metformin treatment is associated with a significant reduction in OM irrespective of diabetes status in patients with EC. The survival benefit suggests that diabetes screening and maintenance of good glycemic control may improve outcomes in EC., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Insulin resistance is common among obese adolescents; however, the extent of this problem is not clear. We conducted a systematic review of PubMed-Medline, CINAHL, The Web of Science, EMBASE and Scopus for observational studies evaluating components defining insulin resistance (insulin, C-peptide and homeostatic model assessment-insulin resistance [HOMA-IR]) in obese adolescents (12-18 years) versus non-obese adolescents. Our systematic review and meta-analysis followed the PRISMA guidelines. Data were combined using a random-effects model and summary statistics were calculated using the mean differences (MDs). 31 studies were included (n = 8655). In 26 studies, fasting insulin levels were higher in obese adolescents when compared to non-obese adolescents (MD = 64.11 pmol/L, 95%CI 49.48-78.75, p < 0.00001). In three studies, fasting C-peptide levels were higher in obese adolescents when compared to non-obese adolescents (MD = 0.29 nmol/L, 95%CI 0.22-0.36, p < 0.00001). In 24 studies, HOMA-IR values were higher in obese adolescents when compared to non-obese adolescents (MD = 2.22, 95%CI 1.78-2.67, p < 0.00001). Heterogeneity of effects among studies was moderate to high. Subgroup analyses showed similar results to the main analyses. Circulating insulin and C-peptide levels and HOMA-IR values were significantly higher in obese adolescents compared to those non-obese.

Background: Insulin resistance (IR) has been implicated in carcinogenesis, but there is no consensus regarding its involvement in ovarian cancer. We performed a systematic review and meta-analysis to evaluate the association between IR and ovarian cancer., Methods: Searches were conducted in five databases for studies evaluating IR markers (levels of serum insulin, C peptide, insulin growth factor [IGF] 1 and IGF-binding proteins [IGFBPs], homeostatic model assessment insulin resistance, and quantitative insulin-sensitivity check index) and ovarian cancer risk. Study selection, data extraction and an assessment of risk of bias were performed independently by three researchers. The associations between IR markers and ovarian cancer were quantified as mean differences (MDs) or standardized MDs (SMDs) and their 95% CIs using random-effects models., Results: Fourteen case-control studies satisfied our inclusion criteria (n=8130). There was little information on IR markers with the exception of the IGF system. Ovarian cancer was associated with lower IGF-1 levels (SMD -0.43ng/mL, 95% CI -0.67 to -0.18; p=0.0006), and lower IGFBP-3 levels (SMD -0.11ng/mL, 95% CI -0.21 to -0.00; p=0.04). However, ovarian cancer was associated with higher levels of IGFBP-2 and IGFBP-1 (MD 527.3ng/mL, 95%CI 473.6, 581.0; p<0.00001, and MD 3.47ng/mL, 95%CI 1.42, 5.52; p=0.0009 respectively). Subgroup analyses by menopausal status and age (≤55 vs >55y) for IGF-1 and IGFBP-3 showed the subgroups were similar, although heterogeneity remained high., Conclusion: The evidence suggests that levels of IGF-1 and IGFBP-3 are lower in patients with ovarian cancer. In contrast, higher levels of IGBP-2 and IGBP-1 are found in patients with ovarian cancer., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: The hormonal manipulation 5-Fluoro-uracil Epirubicin Cyclophosphamide (HMFEC) trial was developed at a time of uncertainty around the dose intensity of chemotherapy given to premenopausal patients with node positive breast cancer and to the benefits of tailored endocrine therapy in such patients., Patients and Methods: HMFEC was a multi-centre, phase III, open label, randomised controlled trial with a 2 × 2 factorial design. Eligible patients were premenopausal with node positive early breast cancer; significant cardiac disease or uncontrolled hypertension was exclusion criterion. Patients were allocated to receive either eight cycles of FE50C or FE75C (given 3 weekly) with or without hormone manipulation (HM; tamoxifen or luteinising hormone releasing hormone (LHRH) agonists according to residual hormone levels at the end of chemotherapy) irrespective of ER status. The primary end-point was disease free survival (DFS). Principal analyses were by intention to treat (ITT); however, to reflect contemporary practice, subgroup analyses according to ER status were also conducted. The mature follow-up now available from this modest sized trial enables presentation of definitive results., Results: Between 1992 and 2000 a total of 785 patients were randomised into the HMFEC trial (203 FE50C-HM, 191 FE50C+HM, 198 FE75C-HM, 193 FE75C+HM). At a median follow-up of 7.4 years, 245 DFS events have been reported (92 ER-, 153 ER+/unknown). The effects on DFS were not statistically significantly different according to epirubicin dose (hazard ratio [HR] = 0.82, 95% confidence interval [CI] 0.63-1.06; p = 0.13 FE75C versus FE50C); however, FE75C appeared to induce more alopecia and neutropenia. No statistically significant evidence was observed to support an improvement in DFS in patients allocated HM either overall (HR = 0.88, 95% CI 0.68-1.13; p = 0.32) or in patients with ER+/unknown disease (HR = 0.85, 95% CI 0.62-1.17; p = 0.32) although effect sizes are consistent with worthwhile clinical effects. Overall, there was no evidence of a difference in survival between any of the four treatment groups of the trial., Conclusion: Higher doses of epirubicin cause more adverse events in the absence of clear improvement in overall survival. Endocrine therapy with either tamoxifen or goserelin provided no significant added benefit to cytotoxic chemotherapy in this group of patients., Trial Registration Number: ISRCTN98335268., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Aim: It has been suggested that chronic hyperinsulinemia from insulin resistance is involved in the etiology of endometrial cancer (EC). We performed a systematic review and meta-analysis to assess whether insulin resistance is associated with the risk of EC., Methods: We searched PubMed-Medline, Embase, Scopus, and Web of Science for articles published from database inception through 30th September 2014. We included all observational studies evaluating components defining insulin resistance in women with and without EC. Quality of the included studies was assessed by Newcastle-Ottawa scale. Random-effects models and inverse variance method were used to meta-analyze the association between insulin resistance components and EC., Results: Twenty-five studies satisfied our inclusion criteria. Fasting insulin levels (13 studies, n = 4088) were higher in women with EC (mean difference [MD] 33.94 pmol/L, 95% confidence interval [CI] 15.04-52.85, p = 0.0004). No differences were seen in postmenopausal versus pre- and postmenopausal subgroup analysis. Similarly, non-fasting/fasting C-peptide levels (five studies, n = 1938) were also higher in women with EC (MD 0.14 nmol/L, 95% CI 0.08-0.21, p < 0.00001). Homeostatic model assessment - insulin resistance (HOMA-IR) values (six studies, n = 1859) in EC patients were significantly higher than in women without EC (MD 1.13, 95% CI 0.20-2.06, p = 0.02). There was moderate-to-high heterogeneity among the included studies., Conclusion: Currently available epidemiologic evidence is suggestive of significantly higher risk of EC in women with high fasting insulin, non-fasting/fasting C-peptide and HOMA-IR values., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Right atrial (RA) enlargement has been associated with worse clinical outcomes in chronic pulmonary hypertension (cPH) patients. Even though current guidelines only recommend measurement of RA dimensions at the end of ventricular systole in these patients, there is paucity of information regarding the potential utility of RA dimensions obtained at the end of ventricular diastole., Methods: In this retrospective study, standard echocardiographic data were collected from 80 studies. The population studied was divided into Group I that consisted of 35 patients (52 ± 10 years) without PH while Group II included 45 patients (56 ± 14 years; P = 0.2) with cPH. RA measurements were obtained not only at the end of ventricular systole, but also at the end of ventricular diastole to determine which RA measurement was more indicative of abnormal right ventricular afterload., Results: Even though all RA measurements were abnormal, RA area (>8.4 cm(2) ) measured at the end of ventricular diastole was the most useful RA variable to identify cPH patients with elevated pulmonary pressures (P < 0.0001) and with an abnormal pulmonary vascular resistance (P = 0.001)., Conclusions: Based on these results, it appears that isolated RA measurements made at the end of ventricular systole are insufficient to fully explain the hemodynamic load of cPH. Additional studies are now required to determine whether sequential monitoring of the composite change in RA dimensions that occur throughout the cardiac cycle over time correlates better with response to vasodilator therapy and overall clinical outcomes., (© 2015, Wiley Periodicals, Inc.)

Systemic sclerosis (SSc) can cause interstitial lung and pulmonary vascular disease that can induce pulmonary arterial hypertension (PAH). It is well known that severe PAH may reduce left ventricluar preload and decrease diastolic filling with the potential of reducing forward flow. We present a case in which a patient with SSc and symptomatic PAH required direct pulmonary vasodilator therapy for treatment of elevated pulmonary pressures. On follow-up echocardiogram, while improvement in right ventricular function and reduction in estimated pulmonary pressures were noted; worsening of aortic valve gradients was also found. Cardiac hemodynamics of pulmonary vasodilator therapy is discussed and the literature is reviewed.

Background: A growing body of evidence seems to suggest that reduction in right ventricular (RV) systolic function is not only associated with both development of symptoms associated with pulmonary arterial hypertension (PAH) but also increased morbidity and adverse clinical outcomes. Recent data suggest that supine bicycle stress echocardiography (sBEE) is feasible and provides realistic resistance and compliance estimations., Methods: The study design was a retrospective analysis of sBEE obtained for clinical indications of dyspnea on exertion or unexplained exercise intolerance. A total of 30 sBEE studies were included. The first 10 sBEE studies served as a calibration cohort not only to establish objective measures of RV performance but also to determine feasibility and reproducibility. The following 20 sBEE served as a validation cohort., Results: Our results demonstrate that tricuspid annular plane systolic excursion and tricuspid annular systolic velocity, even when measured by an untrained reader, are reliable and accurate measures of the RV response to exercise during a sBEE protocol. Furthermore, measurements of RV myocardial performance (Tei index) or peak RV strain during exercise not only are time consuming but also simply unreliable and should not be utilized to evaluate RV function during sBEE., Conclusion: The results of our pilot study suggest that sBEE might be promising for detecting RV abnormalities during exercise. A larger prospective study is now needed to determine if TAPSE and tricuspid annular systolic velocity recorded during sBEE might be useful in assessing patients presenting with dyspnea during exercise or suspected of having PAH., (© 2013, Wiley Periodicals, Inc.)

Background: The severity of pulmonary vascular resistance (PVR) is known to be a critical determinant of right ventricular (RV) systolic function; this relationship remains poorly characterized. We therefore, designed a study to examine the relationship that exists between echocardiographically measured PVR and maximal tricuspid annular plane systolic excursion (TAPSE) to gain some insight regarding RV ejection efficiency (RVEe) in patients with chronic pulmonary hypertension (cPH)., Methods: Standard echocardiographic measures of RV size and systolic performance were recorded from 95 patients (age 54 ± 15 years and pulmonary artery systolic pressures [PASP] that range from 20 to 125 mmHg). For this study, RVEe was defined as TAPSE/Echocardiographic PVR., Results: A strong negative correlation (R(2) = -0.51, P < 0.001) was seen between TAPSE and PASP; however, a power curve trend line fit the relationship between RVEe and PASP (R(2) = 0.77; P < 0.01). In a multiple regression analysis, abnormal pulmonary pressures were better identified when RVEe (P < 0.0001) was used., Conclusions: Based on these results, it appears that measurement of RVEe might be extremely useful for the assessment of RV mechanics and plasticity. The power curve relationship clearly demonstrates that minimal changes in PASP (up to 50 mmHg) result in dramatic reductions in RVEe. A steady decline in RVEe, though at a lower rate, continues to occur with increasing PASP. Additional studies are required using RVEe into a functional RV imaging algorithm and determine if RVEe correlates with development of symptoms, response to therapy and overall clinical outcomes., (© 2013, Wiley Periodicals, Inc.)

Weissella confusa is a Gram-positive bacterium that has been identified in environmental and food samples from around the world. Rare cases of bacteremia in immunocompromised people have been reported. A 2-day-old foal was presented for weakness and suspected sepsis. Blood culture yielded pure growth of a Gram-positive coccobacillus, which was identified as W. confusa through sequencing of the 16S ribosomal DNA. Although the foal initially responded to antimicrobial therapy with ceftiofur and metronidazole, it later developed septic complications of the right tarsocrural joint and right digital flexor tendon sheath and was euthanized. Postmortem examination and histology revealed subcutaneous icterus, severe diffuse interstitial pneumonia, septic synovitis, necrotizing vasculitis with marked thrombosis and hemorrhage in the medial digital vessels of the right hind limb, and ischemic necrosis of the right hind hoof laminae. Gram-positive, coccobacilli were observed in the vascular lesion.

Purpose: The purpose of this work was to validate a new clinical obstetrics and gynecology (OB-GYN) application for a hand-held ultrasound (US) device. We modified the smallest hand-held device on the market and tested the system for transvaginal (TV) use. This device was originally conceived for abdominal scanning only., Methods: The validation involved 80 successive patients examined by the same operator: 25 obstetric and 55 gynecologic cases. US examination was performed transvaginally with two US systems: the hand-held Vscan (General Electrics; GE Vingmed Ultrasound; Norway) for which an intravaginal gadget TTGP-2010® (Troyano transvaginal gadget probe) was designed, and the Voluson 730 Expert (multifrequency transvaginal ultrasound of 3-9MHz; GE Healthcare, Milwaukee, WI, USA). We performed the same measurements with both US systems in order to confirm whether or not their diagnostic capability was similar. Quantitative difference in measurements between the systems was assessed, as well as the overall diagnostic detection rate and suitability for telemedicine., Results: Regarding lesion visibility with Vscan, optimal distance was 8-16cm depending on the examination type, and the total detection rate was 98.7%. The exception was an ovarian endometrioma, diagnosed as a follicular cyst using the hand-held device. Assessment of reproducibility in 180 measurements showed that the measurements obtained with Vscan were 0.3-0.4cm lower than those obtained with the high resolution US device (Voluson 730 Expert). Nevertheless, Pearson's correlation coefficient was high for biparietal diameter (0.72) and gynecological (GYN) (0.99) measurements, and for overall correlation (0.997). Image transport on USB and SD-flash cards proved convenient for telemedicine., Conclusions: A novel TV application of a hand-held US device is demonstrated for OB-GYN. Heart, abdominal and obstetrics presets of the Vscan together with color-Doppler enable a detection capability comparable to that of a high-definition US device. The lower values of the measurements obtained by the hand-held device (by 0.3-0.4cm) must be taken into account, although they have no effect on its diagnostic capability., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Introduction: Pregnancy-induced hypertension (PIH) is a major cause of maternal and perinatal mortality and morbidity, particularly in under-resourced countries, like Mexico. Studies on PIH have shown increased oxidative stress products such as malondialdehyde and decrease of total antioxidant capacity (TAC). In this research we measured one marker of oxidative stress (OS) the TAC in patients with PIH and we associated it with the development of maternal and/or fetal complications., Objectives: Determine whether the plasma level of total antioxidant capacity (as a marker of oxidative stress) influences the development of maternal and/or perinatal complications in patients with PIH., Methods: A observational, analytical, clinical study was conducted in patients with gestational hypertension (GH), mild preeclampsia (MP), severe preeclampsia (SP) and normal pregnancy (NP) > or = 28weeks gestational age. Serum samples were collected and stored at -70°C until use for the determination of total antioxidant capacity. It was associated with the development of maternal and/or perinatal complications., Results: TAC level in normotensive patients (NP) was mean of 2679 +/- 2014mEq/L while in hypertensive patients (GH, MP, SP) was on mean of 1502 +/-1340mEq/L (p<0.05), in the GH group was 1620 +/-1042mEq/L, in the MP group was 1977 +/-1865mEq/L, in the SP was 819 +/-305meq/L The mean TAC level in the 29 patients who had maternal and/or perinatal complications was 1521mEq/L, while in the 38 patients who showed no maternal and/or perinatal complications the mean was 2355mEq/L (p<0.05). Of the 29 patients who had complications 15 (52%) had greatly diminished TAC levels (less than 1000mEq/L), 9 (31%) had between 1000 and 2500mEq/L and only 5 (17%)>2500mEq/L. 72% (28/39) of PIH group had one or more maternal and/or perinatal complications, while only 1 patient (3.6%) of 28 patients with NP had one or more maternal and/or perinatal complications (p<0.05)., Conclusion: Patients with decreased TAC level had a higher percentage of maternal and/or perinatal complications. Patients with PIH classified as mild preeclampsia, showing reduced TAC level should be in close observation as they have the risk of developing life-threatening complications since management is usually as outpatient., (Copyright © 2012. Published by Elsevier B.V.)

Objective: The purpose of the present investigation was to assess sexual function among middle-aged women and determine related risk factors (personal and partner) for sexual dysfunction., Methods: In this cross-sectional study, women aged 40-59 years were requested to fill out the Female Sexual Function Index (FSFI) and a general demographic questionnaire containing personal and partner data., Results: A total of 409 women with a mean age of 47 +/- 5.3 years were surveyed. Of these, 42.1% were premenopausal, 24.4% perimenopausal and 33.5% postmenopausal. At the time of survey, 10.5% of women were hysterectomized, 1.5% used psychotropic drugs, and 9.8% were on hormone therapy (HT) for the menopause; 28.1% had less than 12 years of schooling and 80.4% had only one partner at the moment of survey. Among their male partners, 7.3% abused alcohol, 10.3% had erectile dysfunction, 11.2% premature ejaculation and 63.83% were faithful partners. Mean (+/- standard deviation) scores for the FSFI domains were: desire (3.7 +/- 1.2), arousal (3.1 +/- 2.5), lubrication (3.3 +/- 2.6), orgasm (2.6 +/- 2.3), satisfaction (4 +/- 1.7), and pain/dyspareunia (3.2 +/- 2.6). The mean total FSFI score was 20.1 +/- 12.4 (median 24.7). In this series, the prevalence of female sexual dysfunction (FSFI score

Matrix metalloproteinase-2 (MMP-2) is an enzyme with proteolytic activity on matrix proteins, and previous studies have revealed a strong association between the MMP-2 -1306C-->T polymorphism and the risk of several types of cancer. Our study looked at whether this polymorphism contributed to the development of cervical neoplasia by analyzing 54 patients with invasive squamous cell cervical cancer, 100 patients with cervical intraepithelial neoplasia, and 126 control subjects. The MMP-2 CC genotype was more frequent in the cancer patients when compared with the control group (OR 2.57; 95% CI 1.15-5.86). The association of cervical cancer with the CC genotype was more pronounced in women who had first coitus at an early age (OR 3.96; 95% CI 1.46-11.06). The CC genotype was associated with intraepithelial neoplasia only in women with first coitus at 19 years old or younger. The data suggest that the MMP-2 -1306C-->T polymorphism contributes to the development of squamous cell cervical cancer in the population studied, especially in women who had first coitus at an early age.

Background: Matrix metalloproteinase-2 (MMP-2) is an enzyme with proteolytic activity on matrix proteins, particularly basement membrane constituents. A single nucleotide polymorphism C>T transition at -1306 displayed a strong association with several cancers. Our study investigated whether or not the MMP-2 -1306C>T polymorphism contributed to the development of breast cancer (BC) in a Mexican population., Methods: 90 patients with BC and 96 control subjects were analyzed to detect MMP-2 -1306C>T polymorphism., Results: The frequency of MMP-2 CC genotype was significantly higher in BC patients when compared with the control group (OR 2.15; 95% CI 1.1-4.1). MMP-2 CC genotype frequency was more pronounced in younger subjects (< or =50 years) at diagnosis (OR 2.66; 95% CI 1.04-6.96)., Conclusion: The data suggest that MMP-2 -1306C>T polymorphism strongly contributes to the development of BC in the population studied, especially among women 50 years old and younger., ((c) 2008 S. Karger AG, Basel)

Serum levels of prolactin (PRL), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured in normally cycling women and normal men before and after oral admiministration of 1 mg of clebopride, a derivative of procainamide used in the treatment of gastrointestinal diseases. Clebopride produced a significant increase (P < 0.001) in serum PRL to a 6-fold peak as compared with basal levels. After 240 minutes the levels remained significantly higher (P < 0.05) than the mean basal level at -30 and 0 minutes. No significant effects of clebopride were noted upon the circulating levels of LH and FSH. The peak PRL response to clebopride was unaffected by pretreatment with 100 mg of nomifensine, although the secretory area from 120 to 210 minutes after clebopride was greater (P < 0.05) in the nomifensine-treated group than in the control experiment. When 5 mg of bromocriptine were given before clebopride, the PRL response was completely abolished as compared with the control experiment (P < 0.001). Our data provide new evidence that dopaminergic receptors of the adeylate cyclase system are involved in the regulation of PRL secretion, acting at the pituitary level rather than acting on the hypothalamus. The PRL-releasing activity of clebopride could be the explanation for the occasional menstrual disorders and galactorrhea registered in some cases of long-term treatment.

Physiologic and pathologic production of milk involves complex relations between the mammary glands, hormones, and the central nervous system. In all the galactorrhea syndromes there is a functional or mechanical problem at the pituitary level, with abnormal secretion or reserve of prolactin secretion. Stimulatory agents of prolactin, like thyrotropin releasing hormone (TRH), chlorpromazine, amnio acids, and insulin, can be helpful in the study of the hypothalamic pituitary functional reserve, while the osmotic tests seem to provide a clear distinction between functional and tumoral causes. The inhibitory agents of prolactin secretion, L-dopa and CB 154, permit the study of the negative control of the hormone. In addition, CB 154 appears to be an effective treatment for functional galactorrhea. Hyperprolactinemia appears to exert an inhibitory influence on gonadotropins. Clomiphene, acting on the hypothalamus, and LHRH, acting on the gonadotropes, permit the assessment of the gonadotropic hypothalamic-hypophyseal axis.

Using a new antiserum, an enzymatic radioiodination of arginine vasopressin (AVP), and the methodology of Robertson et al. (1,2), we have developed a sensitive and specific radioimmunoassay for plasma AVP in the monkey. The sensitivity of the assay is 0.5 muU/ml, the cross reaction with oxytocin (OT), minimal. We used this assay to study the effects that variations in blood osmolality have in regulating AVP secretion in unanesthetized, chair-restrained, chamber-isolated, adult female rhesus monkeys. Under water ad lib conditions, plasma AVP and osmolality were relatively constant, averaging 1.7 +/- 0.6 (SD) muU/ml and 298 +/- 3 mosmol/kg, respectively. Water loading decreased plasma AVP and osmolality to 0.6 +/- 0.2 muU/ml and 282 +/- 6 mosmol/kg, respectively. When fluid restriction increased osmolality, plasma AVP rose progressively to twice the baseline after 1 day, and to 6 times the baseline after 3 days. The rise in plasma AVP was linearly correlated with the rise in osmolality (r = 0.93; P less than 0.001). Intravenous infusions of hypertonic saline produced significant rises in plasma osmolality and plasma AVP. There was a dose-related rise in plasma AVP that declined later at the expected rate with the infusion of physiological amounts of synthetic AVP.

To evaluate a possible role of the amygdala (Amyg) in the neural control of arginine vasopressin (AVP) release, adult female monkeys (Macaca mulatta) with electrodes chronically implanted in the Amyg, hypothalamus and pituitary gland were given 5% dextrose and water infusions and were stimulated electrically at these sites. Immediately before and after, and at 5, 10, 15 and 30 min intervals following electrical stimulation, blood samples were withdrawn from unanesthetized monkeys, through implanted cardiac cannulae, for radioimmunoassay (RIA) of plasma AVP and for plasma osmolality determination. In the Amyg-stimulated monkeys, plasma AVP rose rapidly to peak values at the end of stimulation followed by an abrupt post-stimulation fall to control levels in 30 min. A small yet significant rise in plasma osmolality was also observed. Electrical stimulation of the hypothalamus and the pituitary gland yielded a temporal pattern of plasma AVP rise and fall identical to that seen following Amyg stimulation. Blood sampling, precisely timed to the onset and end of the stimulus train, was important in capturing the rise and fall in plasma AVP. Stimulus intensity determined the magnitude of plasma AVP elevation at each of these sites, with the highest current densities yielding the highest levels of plasma AVP. It is suggested that the Amyg may be involved in the neural triggering of AVP release from the neurohypophysis.