Resource Competition May Lead to Effective Treatment of Antibiotic Resistant Infections

Drug resistance is a common problem in the fight against infectious diseases. Recent studies have shown conditions (which we call antiR) that select against resistant strains. However, no specific drug administration strategies based on this property exist yet. Here, we mathematically compare growth of resistant versus sensitive strains under different treatments (no drugs, antibiotic, and antiR), and show how a precisely timed combination of treatments may help defeat resistant strains. Our analysis is based on a previously developed model of infection and immunity in which a costly plasmid confers antibiotic resistance. As expected, antibiotic treatment increases the frequency of the resistant strain, while the plasmid cost causes a reduction of resistance in the absence of antibiotic selection. Our analysis suggests that this reduction occurs under competition for limited resources. Based on this model, we estimate treatment schedules that would lead to a complete elimination of both sensitive and resistant strains. In particular, we derive an analytical expression for the rate of resistance loss, and hence for the time necessary to turn a resistant infection into sensitive (tclear). This time depends on the experimentally measurable rates of pathogen division, growth and plasmid loss. Finally, we estimated tclear for a specific case, using available empirical data, and found that resistance may be lost up to 15 times faster under antiR treatment when compared to a no treatment regime. This strategy may be particularly suitable to treat chronic infection. Finally, our analysis suggests that accounting explicitly for a resistance-decaying rate may drastically change predicted outcomes in host-population models

Statin use and incident cardiovascular events in renal transplant recipients

BACKGROUND: Statins achieve potent LDL lowering in the general population leading to a significant cardiovascular (CV) risk reduction. In renal transplant recipients (RTR) statins are included in treatment guidelines, however, conclusive evidence of improved cardiovascular outcomes has not been uniformly provided and concerns have been raised about simultaneous use of statins and the immunosuppressant cyclosporine. This study aimed to elucidate the effect of statins on a compound CV endpoint, comprised of ischaemic CV events and CV mortality in RTR, with subgroup analysis focussing on cyclosporine users. METHOD: 622 included RTR (follow‐up 5.4 years) were matched based on propensity scores and dichotomized by statin use. Survival analysis was conducted. RESULTS: Cox regression showed that statin use was not significantly associated with the compound CV endpoint in a fully adjusted model (HR = 0.81, 95% CI = 0.53‐1.24, P = .33). Subgroup analyses in RTR using cyclosporine revealed a strong positive association of statin use with the CV compound outcome in a fully adjusted model (HR = 6.60, 95% CI 1.75‐24.9, P = .005). Furthermore, statin use was positively correlated with cyclosporine trough levels (correlation coefficient 0.11, P = .04). CONCLUSION: In conclusion, statin use does not significantly decrease incident CV events in an overall RTR cohort, but is independently associated with CV‐specific mortality and events in cyclosporine using RTR, possibly due to a bilateral pharmacological interaction

Flexible random lasers in dye-doped bio-degradable cellulose nanocrystalline needles

M-ERA-NET2/0007/2016 POCI-01-0145-FEDER-007688 PTDC/CTM-BIO/6178/2014 PTDC/CTM-REF/30529/2017 UID/CTM/50025In this work, we developed and investigated a random laser based on rhodamine6G (Rh6G) in ethylene glycol (EG) solution with varying cellulose nanocrystalline (CNC) needles as scatterers in the lasing media. Besides the suspension-in-cuvette scheme, an alternative configuration was also employed: a dye-CNC flexible self-supported thick-film (70 µm) random laser made by drop casting of the CNCs + Rh6G + hydroxypropyl cellulose suspension. In relation to conventional scatterers, the biodegradable cellulose nanocompounds showed a comparable reduction in both the spectral full width at half-maximum and the energy threshold values, with an optimal concentration of 5 mg [CNC]/ml[EG] in suspension. Its performance was also compared with other cellulose-based random lasers, presenting advantages for some parameters. The flexible film configuration showed similar results, but contained 10% less Rh6G than the suspension.authorsversionpublishe

Physical Activity and the Development of Post-Transplant Diabetes Mellitus, and Cardiovascular- and All-Cause Mortality in Renal Transplant Recipients

(1) Background: Little is currently known about the health impacts of daily-life moderate-to-vigorous physical activity (MVPA) in relation to the development of post-transplant diabetes mellitus (PTDM) and the long-term survival of renal transplant recipients (RTRs). (2) Methods: We analyzed self-reported data on MVPA within non-occupational and occupational domains, estimated with the SQUASH questionnaire, from a prospective cohort study of RTRs (n = 650) with a functioning graft exceeding 1 year. PTDM diagnoses were based on plasma glucose levels (>= 126 mg/dL), HbA1c (>= 6.5%), and the use of antidiabetic medication. Mortality data were retrieved from patient files up to the end of September 2015. (3) Results: During a median follow-up period of 5.3 years, 50 patients (10%) developed PTDM and 129 (19.8%) died. Of these deaths, 53 (8.9%) were caused by cardiovascular disease. Cox regression analyses showed that higher MVPA levels among patients were associated with a lower risk of PTDM (hazard ratio (HR); 95% confidence interval (95%CI) = 0.49; 0.25-0.96, p = 0.04), cardiovascular- (0.34; 0.15-0.77, p = 0.01), and all-cause mortality (0.37; 0.24-0.58, p <0.001) compared with No-MVPA patients, independently of age, sex, and kidney function parameters. Associations of MVPA with cardiovascular and all-cause mortality remained significant and materially unchanged following further adjustments made for transplant characteristics, lifestyle factors, metabolic parameters, medication use, and creatinine excretion (muscle mass). However, the association between MVPA and PTDM was no longer significant after we adjusted for metabolic confounders and glucose levels. (4) Conclusion: Higher MVPA levels are associated with long-term health outcomes in RTRs

Meaning of the Pap smear for health student

OBJECTIVE: To describe the meanings of the Pap smear for health students. METHODS: Descriptive study, qualitative approach, with 45 students from the health area of ​​a Higher Education Institution, in the Northeast of Brazil. Data were collected in 2017, by means of interviews, processed in the IRaMuTeQ software, and pushed by the Descending Hierarchical Classification. RESULTS: The students recognize that the education in health is the best strategy to prevent cervical cancer, as it is an essential tool in primary care and must be performed by health professionals. CONCLUSION: The meanings found by the students revealed a concern with their role in the Pap smear and, therefore, considers it very important to improve their knowledge in this area so that they can provide quality care to women seeking to prevent cervical cancer.OBJETIVO: Descrever os significados do exame de Papanicolaou para estudantes da saúde. MÉTODOS: Estudo descritivo, de abordagem qualitativa, com 45 estudantes da área de saúde de uma Instituição de Ensino Superior, no Nordeste do Brasil. Os dados foram coletados em 2017, por meio de entrevistas, processados no software IRaMuTeQ, e analisados pela Classificação Hierárquica Descendente. RESULTADOS: Os estudantes reconhecem que a educação em saúde é a melhor estratégia para prevenir o cancro do colo do útero, por ser uma ferramenta essencial na atenção básica e deve ser realizada por profissionais de saúde. CONCLUSÃO: Os significados atribuídos pelos estudantes revelaram uma preocupação com seu papel no exame de Papanicolaou e, portanto, consideram muito importante aprimorar seus conhecimentos nessa área para que possam prestar um atendimento de qualidade às mulheres que buscam a prevenção do cancro de colo do úteroinfo:eu-repo/semantics/publishedVersio

Personalized dynamic phantom of the right and left ventricles based on patient-specific anatomy for echocardiography studies — Preliminary results

Dynamic phantoms of the heart are becoming a reality, with their use spread across both medical and research fields. Their purpose is to mimic the cardiac anatomy, as well as its motion. This work aims to create a dynamic, ultrasound-compatible, realistic and flexible phantom of the left and right ventricles, with application in the diagnosis, planning, treatment and training in the cardiovascular field for studies using echocardiography. Here, we focus on its design and production with polyvinyl alcohol cryogel (PVA-C), to be assembled with a pump and an electromechanical (E/M) system in a water tank. Based on a patient-specific anatomical model and produced using a 3D printing technique and molding, the PVA-C phantom mimics the ventricles' natural anatomy and material properties, while the pump and E/M systems mimic the natural movements and pressures. The PVA-C phantom was assessed by imaging and measuring it using a four-dimensional ultrasound machine. The PVA-C phantom demonstrated to be a versatile option to produce patient-specific biventricular models, preserving their shape after manufacturing and presenting good echogenic properties. Both chambers were clearly seen in the ultrasound images, together with the interventricular septum and the myocardial wall. Automated left ventricle measures revealed a decrease of its volume with regard to the designed model (98 ml to 74 ml). Overall, the preliminary results are satisfactory and encourage its use for the abovementioned purposesFEDER funds through the Competitiveness Factors Operational Programme (COMPETE), and by National funds through the Foundation for Science and Technology (FCT) under the project POCI -01-0145-FEDER-007038 and EXPL/BBB-BMD/2473/2013, and by the projects NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-024300, supported by the NORTE 2020, under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). J. Gomes-Fonseca, P. Morais, S. Queirós, and F. Veloso were funded by FCT under the Ph.D. grants PD/BDE/113597/2015, SFRH/BD/95438/2013, SFRH/BD/93443/2013, and SFRH/BD/131545/2017info:eu-repo/semantics/publishedVersio

Algorithm for the treatment of type 2 diabetes: a position statement of Brazilian Diabetes Society

The Brazilian Diabetes Society is starting an innovative project of quantitative assessment of medical arguments of and implementing a new way of elaborating SBD Position Statements. The final aim of this particular project is to propose a new Brazilian algorithm for the treatment of type 2 diabetes, based on the opinions of endocrinologists surveyed from a poll conducted on the Brazilian Diabetes Society website regarding the latest algorithm proposed by American Diabetes Association /European Association for the Study of Diabetes, published in January 2009

Malnutrition according to GLIM criteria in stable renal transplant recipients:Reduced muscle mass as predominant phenotypic criterion

Background & aims: Malnutrition has a negative impact on quality of life and survival in renal transplant recipients (RTR). Therefore, malnutrition detection is important in RTR, but this may be hampered by concomitant presence of weight gain and overweight. Recently, the Global Leadership Initiative on Malnutrition (GLIM) developed a set of diagnostic criteria for malnutrition. We aimed to assess the prevalence of malnutrition according to the GLIM criteria and the distribution of phenotypic criteria in RTR. Additionally, we examined the potential value of 24-h urinary creatinine excretion rate (CER) as alternative measure for the criterion reduced muscle mass. Methods: We used data from stable outpatient RTR included in the TransplantLines Cohort and Biobank Study (NCT02811835). Presence of weight loss and reduced intake or assimilation were derived from Patient-Generated Subjective Global Assessment (PG-SGA) item scores. Reduced muscle mass was assessed by multi-frequency bio-electrical impedance analysis (MF-BIA) and defined as an appendicular skeletal muscle mass index (ASMI) < 7 kg/m(2) for men and 5 mg/L. Malnutrition was defined as presence of at least one phenotypic (weight loss and/or low BMI and/or reduced muscle mass) and one etiologic criterion (reduced intake/assimilation and/or disease burden/inflammation). Results: We included 599 RTR (55 +/- 13 years old, 62% male, BMI 27.2 +/- 4.7 kg/m(2)) at a median of 3.1 years after transplantation. According to GLIM criteria, 14% was malnourished, of which 91% met the phenotypic criterion for reduced muscle mass. Similar results were found by using CHI as measure for muscle mass (13% malnutrition of which 79% with reduced muscle mass). Conclusions: Malnutrition is present in one in 7 stable RTR, with reduced muscle mass as the predominant phenotypic criterion. Assessment of nutritional status, most importantly muscle status, is warranted in routine care, to prevent malnutrition in RTR from remaining undetected and untreated. The diagnostic value of 24-h urinary CER in this regard requires further investigation. (C) 2020 The Author(s). Published by Elsevier Ltd

Inheritance of DNA Transferred from American Trypanosomes to Human Hosts

Interspecies DNA transfer is a major biological process leading to the accumulation of mutations inherited by sexual reproduction among eukaryotes. Lateral DNA transfer events and their inheritance has been challenging to document. In this study we modified a thermal asymmetric interlaced PCR by using additional targeted primers, along with Southern blots, fluorescence techniques, and bioinformatics, to identify lateral DNA transfer events from parasite to host. Instances of naturally occurring human infections by Trypanosoma cruzi are documented, where mitochondrial minicircles integrated mainly into retrotransposable LINE-1 of various chromosomes. The founders of five families show minicircle integrations that were transferred vertically to their progeny. Microhomology end-joining of 6 to 22 AC-rich nucleotide repeats in the minicircles and host DNA mediates foreign DNA integration. Heterogeneous minicircle sequences were distributed randomly among families, with diversity increasing due to subsequent rearrangement of inserted fragments. Mosaic recombination and hitchhiking on retrotransposition events to different loci were more prevalent in germ line as compared to somatic cells. Potential new genes, pseudogenes, and knockouts were identified. A pathway of minicircle integration and maintenance in the host genome is suggested. Thus, infection by T. cruzi has the unexpected consequence of increasing human genetic diversity, and Chagas disease may be a fortuitous share of negative selection. This demonstration of contemporary transfer of eukaryotic DNA to the human genome and its subsequent inheritance by descendants introduces a significant change in the scientific concept of evolutionary biology and medicine

Post-transplant obesity impacts long-term survival after liver transplantation

Background: Short-term survival after orthotopic liver transplantation (OLT) has improved over the past decades, but long-term survival remains impaired. The effects of obesity on long-term survival after OLT are controversial. Because pre-transplant body mass index (BMI) can be confounded by ascites, we hypothesized that post-transplant BMI at 1 year could predict long-term survival. Methods: A post-hoc analysis was performed of an observational cohort study consisting of adult recipients of a first OLT between 1993 and 2010. Baseline BMI was measured at 1-year post-transplantation to represent a stable condition. Recipients were stratified into normal weight (BMI 30 kg/m2). Kaplan-Meier survival analyses were performed with log-rank testing, followed by multivariable Cox proportional hazards regression analysis. Results: Out of 370 included recipients, 184 had normal weight, 136 were overweight, and 50 were obese at 1-year post-transplantation. After median follow-up for 12.3 years, 107 recipients had died, of whom 46 (25%) had normal weight, 39 (29%) were overweight, and 22 (44%) were obese (log-rank P = 0.020). Obese recipients had a significantly increased mortality risk compared to normal weight recipients (HR 2.00, 95% CI 1.08–3.68, P = 0.027). BMI was inversely associated with 15 years patient survival (HR 1.08, 95% CI 1.03–1.14, P = 0.001 per kg/m2), independent of age, gender, muscle mass, transplant characteristics, cardiovascular risk factors, kidney- and liver function. Conclusion: Obesity at 1-year post-transplantation conveys a 2-fold increased mortality risk, which may offer potential for interventional strategies (i.e. dietary advice, lifestyle modification, or bariatric surgery) to improve long-term survival after OLT