Lipidomics Reveals Reduced Inflammatory Lipid Species and Storage Lipids after Switching from EFV/FTC/TDF to RPV/FTC/TDF: A Randomized Open-Label Trial

HIV and antiretroviral therapy affect lipid metabolism. Lipidomics quantifies several individual species that are overlooked using conventional biochemical analyses, outperforming traditional risk equations. We aimed to compare the plasma lipidomic profile of HIV patients taking efavirenz (EFV) or rilpivirine (RPV). Patients >/= 18 years old on EFV co-formulated with emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) with HIV-RNA /=6 months were randomized to continue EFV/FTC/TDF (n = 14) or switch to RPV/FTC/TDF (n =15). Lipidomic analyses conducted by mass spectrometry (MS) were performed at baseline and after 12 and 24 weeks. OWLiver((R)) Care and OWLiver((R)) tests were performed to estimate the presence of fatty liver disease (NAFLD). No significant differences (83% male, median age 44 years, 6 years receiving EFV/FTC/TDF, CD4(+) count 740 cells/mm(3), TC 207 [57 HDL-C/133 LDL-C] mg/dL, TG 117 mg/dL) were observed between the groups at baseline. Significant reductions in plasma lipids and lipoproteins but increased circulating bilirubin concentrations were observed in patients who switched to RPV/FTC/TDF. Patients on RPV/FTC/TDF showed a decrease in the global amount of storage lipids (-0.137 log2 [fold-change] EFV vs. 0.059 log2 [fold-change] RPV) but an increase in lysophosphatidylcholines (LPCs) and total steroids. Compared with EFV, RPV increased metabolites with anti-inflammatory properties and reduced the repository of specific lipotoxic lipids

Mechanisms of Tolerance and Resistance to Chlorhexidine in Clinical Strains of Klebsiella pneumoniae Producers of Carbapenemase: Role of New Type II Toxin-Antitoxin System, PemIK

Although the failure of antibiotic treatment is normally attributed to resistance, tolerance and persistence display a significant role in the lack of response to antibiotics. Due to the fact that several nosocomial pathogens show a high level of tolerance and/or resistance to chlorhexidine, in this study we analyzed the molecular mechanisms associated with chlorhexidine adaptation in two clinical strains of Klebsiella pneumoniae by phenotypic and transcriptomic studies. These two strains belong to ST258-KPC3 (high-risk clone carrying β-lactamase KPC3) and ST846-OXA48 (low-risk clone carrying β-lactamase OXA48). Our results showed that the K. pneumoniae ST258-KPC3CA and ST846-OXA48CA strains exhibited a different behavior under chlorhexidine (CHLX) pressure, adapting to this biocide through resistance and tolerance mechanisms, respectively. Furthermore, the appearance of cross-resistance to colistin was observed in the ST846-OXA48CA strain (tolerant to CHLX), using the broth microdilution method. Interestingly, this ST846-OXA48CA isolate contained a plasmid that encodes a novel type II toxin/antitoxin (TA) system, PemI/PemK. We characterized this PemI/PemK TA system by cloning both genes into the IPTG-inducible pCA24N plasmid, and found their role in persistence and biofilm formation. Accordingly, the ST846-OXA48CA strain showed a persistence biphasic curve in the presence of a chlorhexidine-imipenem combination, and these results were confirmed by the enzymatic assay (WST-1).The State Plan for R+D+I 2013–2016 National Plan for Scientific Research, Technological Development and Innovation 2008–2011 PI16/01163 and PI19/00878ISCIII-Deputy General Directorate for Evaluation and Promotion of Research - European Regional Development Fund “A way of Making Europe” and Instituto de Salud Carlos III FEDER, Spanish Network for the Research in Infectious Diseases REIPI, RD16/0016/0001, RD16/CIII/0004/0002 and RD16/0016/0006The Study Group on Mechanisms of Action and Resistance to Antimicrobials, GEMAR

No additional value of conventional and high-sensitivity cardiac troponin over clinical scoring systems in the differential diagnosis of type 1 versus type 2 myocardial infarction.

BACKGROUND: The distinction of type 1 and type 2 myocardial infarction (MI) is of major clinical importance. Our aim was to evaluate the diagnostic ability of absolute and relative conventional cardiac troponin I (cTnI) and high-sensitivity cardiac troponin T (hs-cTnT) in the distinction between type 1 and type 2 MI in patients presenting at the emergency department with non-ST-segment elevation acute chest pain within the first 12 h. METHODS: We measured cTnI (Dimension Vista) and hs-cTnT (Cobas e601) concentrations at presentation and after 4 h in 200 patients presenting with suspected acute MI. The final diagnosis, based on standard criteria, was adjudicated by two independent cardiologists. RESULTS: One hundred and twenty-five patients (62.5%)were classified as type 1 MI and 75 (37.5%) were type 2 MI. In a multivariable setting, age (relative risk [RR]=1.43, p=0.040), male gender (RR=2.22, p=0.040), T-wave inversion (RR=8.51, p<0.001), ST-segment depression (RR=8.71, p<0.001) and absolute delta hs-cTnT (RR=2.10, p=0.022) were independently associated with type 1 MI. In a receiver operating characteristic curve analysis, the discriminatory power of absolute delta cTnI and hs-cTnT was significantly higher compared to relative c-TnI and hs-cTnT changes. The additive information provided by cTnI and hs-cTnT over and above the information provided by the "clinical" model was only marginal. CONCLUSIONS: The diagnostic information provided by serial measurements of conventional or hs-cTnT is not better than that yielded by a simple clinical scoring model. Absolute changes are more informative than relative troponin changes

Evaluación ambiental y planificación de la expansión agropecuaria y forestal en la cuenca del río Miriñay

La cuenca del río Miriñay en la provincia de Corrientes constituye un área de creciente actividad económica en relación con el cultivo de arroz. Con el objetivo de evaluar ambientalmente la realización y acumulación de proyectos agropecuarios y forestales en la cuenca, se consideró el consumo de agua y la pérdida de ambientes naturales tanto de los proyectos ya realizados como de las posibilidades de expansión a futuro. Se elaboraron mapas de cobertura del suelo para los años 2000 y 2014 a partir de imágenes satelitales. Se desarrolló un modelo hidrológico con el cual se simuló un escenario natural, representativo de las condiciones anteriores al cambio del uso del suelo. Se generaron tres escenarios de expansión considerando la construcción de nuevas represas para riego de arroz y el desarrollo de otras actividades productivas. Al año 2014 las áreas transformadas representaban 12,9% de la cuenca, con 114.260 ha de arroz/pasturas, 15.058 ha de embalses y 26.745 ha de forestaciones. Comparando los indicadores de balance hídrico entre el escenario natural y el actual se observaron variaciones de distinto signo y magnitud en las diferentes subcuencas, con disminuciones que no superan el 8% y aumentos que no llegan al 2%. Del análisis de la pérdida de ambientes naturales en los escenarios futuros se observó que, si bien a nivel de toda la cuenca no pareciera superarse un límite crítico, tres subcuencas llegan a muy altos niveles de transformación en el escenario a largo plazo. Para esos escenarios los cambios en el balance hídrico anual serán relativamente menores. Con el propósito de mitigar el impacto de la pérdida de ambientes naturales, se propone la planificación integrada y el ordenamiento territorial de la cuenca a través de la regulación del porcentaje máximo de cambio de uso del suelo, permitiendo así desarrollar el potencial productivo sin poner en riesgo la conservación de los ambientes naturales.Gerencia de Comunicación e Imagen InstitucionalFil: Guizburg, Rubén G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ecología, Genética y Evolución. Grupo de Estudios de Sistemas Ecológicos en Ambientes Agrícolas; ArgentinaFil: Torrella, Sebastián A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ecología, Genética y Evolución. Grupo de Estudios de Sistemas Ecológicos en Ambientes Agrícolas; ArgentinaFil: Menéndez, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ecología, Genética y Evolución. Grupo de Estudios de Sistemas Ecológicos en Ambientes Agrícolas; ArgentinaFil: Sabarots Gerbec, Martín. Instituto Nacional del Agua. Laboratorio de Hidráulica; Argentina. Universidad de Buenos Aires. Facultad de Ingeniería; ArgentinaFil: Adámoli, Jorge. Instituto Nacional del Agua. Laboratorio de Hidráulica; Argentina. Universidad de Buenos Aires. Facultad de Ingeniería; ArgentinaFil: Rujana, Mario Rubén. Instituto Correntino del Agua y del Ambiente; Argentina. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias; Argentin

Synergistic impact of endurance training and intermittent hypobaric hypoxia on cardiac function and mitochondrial energetic and signaling

Background Intermittent hypobaric-hypoxia (IHH) and endurance-training (ET) are cardioprotective strategies against stress-stimuli. Mitochondrial modulation appears to be an important step of the process. This study aimed to analyze whether a combination of these approaches provides additive or synergistic effects improving heart-mitochondrial and cardiac-function. Methods Two-sets of rats were divided into normoxic-sedentary (NS), normoxic-exercised (NE, 1 h/day/5 weeks treadmill-running), hypoxic-sedentary (HS, 6000 m, 5 h/day/5 weeks) and hypoxic-exercised (HE) to study overall cardiac and mitochondrial function. In vitro cardiac mitochondrial oxygen consumption and transmembrane potential were evaluated. OXPHOS subunits and ANT protein content were semi-quantified by Western blotting. HIF-1α, VEGF, VEGF-R1 VEGF-R2, BNP, SERCA2a and PLB expressions were measured by qRT-PCR and cardiac function was characterized by echocardiography and hemodynamic parameters. Results Respiratory control ratio (RCR) increased in NE, HS and HE vs. NS. Susceptibility to anoxia/reoxygenation-induced dysfunction decreased in NE, HS and HE vs. NS. HS decreased mitochondrial complex-I and -II subunits; however HE completely reverted the decreased content in complex-II subunits. ANT increased in HE. HE presented normalized ventricular–arterial coupling (Ea) and BNP myocardial levels and significantly improved myocardial performance as evaluated by increased cardiac output and normalization of the Tei index vs. HS. Conclusion Data demonstrates that IHH and ET confer cardiac mitochondria with a more resistant phenotype although without visible addictive effects at least under basal conditions. It is suggested that the combination of both strategies, although not additive, results into improved cardiac function

A new surgical model of skeletal muscle injuries in rats reproduces human sports lesions

Skeletal muscle injuries are the most common sports-related injuries in sports medicine. In this work, we have generated a new surgically-induced skeletal muscle injury in rats, by using a biopsy needle, which could be easily reproduced and highly mimics skeletal muscle lesions detected in human athletes. By means of histology, immunofluorescence and MRI imaging, we corroborated that our model reproduced the necrosis, inflammation and regeneration processes observed in dystrophic mdx-mice, a model of spontaneous muscle injury, and realistically mimicked the muscle lesions observed in professional athletes. Surgically-injured rat skeletal muscles demonstrated the longitudinal process of muscle regeneration and fibrogenesis as stated by Myosin Heavy Chain developmental (MHCd) and collagen-I protein expression. MRI imaging analysis demonstrated that our muscle injury model reproduces the grade I-II type lesions detected in professional soccer players, including edema around the central tendon and the typically high signal feather shape along muscle fibers. A significant reduction of 30% in maximum tetanus force was also registered after 2 weeks of muscle injury. This new model represents an excellent approach to the study of the mechanisms of muscle injury and repair, and could open new avenues for developing innovative therapeutic approaches to skeletal muscle regeneration in sports medicin

Treatment challenges in and outside a specialist network setting: Pancreatic neuroendocrine tumours

Pancreatic Neuroendocrine Neoplasms comprise a group of rare tumours with special biology, an often indolent behaviour and particular diagnostic and therapeutic requirements. The specialized biochemical tests and radiological investigations, the complexity of surgical options and the variety of medical treatments that require individual tailoring, mandate a multidisciplinary approach that can be optimally achieved through an organized network. The present study describes currents concepts in the management of these tumours as well as an insight into the challenges of delivering the pathway in and outside a Network

Testicular germ-cell tumours and penile squamous cell carcinoma: Appropriate management makes the difference

Germ-cell tumours (GCT) of the testis and penile squamous cell carcinoma (PeSCC) are a rare and a very rare uro-genital cancers, respectively. Both tumours are well defined entities in terms of management, where specific recommendations - in the form of continuously up-to-dated guide lines-are provided. Impact of these tumour is relevant. Testicular GCT affects young, healthy men at the beginning of their adult life. PeSCC affects older men, but a proportion of these patients are young and the personal consequences of the disease may be devastating. Deviation from recommended management may be a reason of a significant prognostic worsening, as proper treatment favourably impacts on these tumours, dramatically on GCT and significantly on PeSCC. RARECAREnet data may permit to analyse how survivals may vary according to geographical areas, histology and age, leading to assume that non-homogeneous health-care resources may impact the cure and definitive outcomes. In support of this hypothesis, some epidemiologic datasets and clinical findings would indicate that survival may improve when appropriate treatments are delivered, linked to a different accessibility to the best health institutions, as a consequence of geographical, cultural and economic barriers. Finally, strong clues based on epidemiological and clinical data support the hypothesis that treatment delivered at reference centres or under the aegis of a qualified multi-institutional network is associated with a better prognosis of patients with these malignancies. The ERN EURACAN represents the best current European effort to answer this clinical need

Treatment challenges in and outside a network setting: Head and neck cancers

Head and neck cancer (HNC) is a rare disease that can affect different sites and is characterized by variable incidence and 5-year survival rates across Europe. Multiple factors need to be considered when choosing the most appropriate treatment for HNC patients, such as age, comorbidities, social issues, and especially whether to prefer surgery or radiation-based protocols. Given the complexity of this scenario, the creation of a highly specialized multidisciplinary team is recommended to guarantee the best oncological outcome and prevent or adequately treat any adverse effect. Data from literature suggest that the multidisciplinary team-based approach is beneficial for HNC patients and lead to improved survival rates. This result is likely due to improved diagnostic and staging accuracy, a more efficacious therapeutic approach and enhanced communication across disciplines. Despite the benefit of MTD, it must be noted that this approach requires considerable time, effort and financial resources and is usually more frequent in highly organized and high-volume centers. Literature data on clinical research suggest that patients treated in high-accrual centers report better treatment outcomes compared to patients treated in low-volume centers, where a lower radiotherapy-compliance and worst overall survival have been reported. There is general agreement that treatment of rare cancers such as HNC should be concentrated in high volume, specialized and multidisciplinary centers. In order to achieve this goal, the creation of international collaboration network is fundamental. The European Reference Networks for example aim to create an international virtual advisory board, whose objectives are the exchange of expertise, training, clinical collaboration and the reduction of disparities and enhancement of rationalize migration across Europe. The purpose of our work is to review all aspects and challenges in and outside this network setting planned for the management of HNC patients

Identification of COVID-19 patients at risk of hospital admission and mortality: a European multicentre retrospective analysis of mid-regional pro-adrenomedullin

Background: Mid-Regional pro-Adrenomedullin (MR-proADM) is an inflammatory biomarker that improves the prognostic assessment of patients with sepsis, septic shock and organ failure. Previous studies of MR-proADM have primarily focussed on bacterial infections. A limited number of small and monocentric studies have examined MR-proADM as a prognostic factor in patients infected with SARS-CoV-2, however there is need for multicenter validation. An evaluation of its utility in predicting need for hospitalisation in viral infections was also performed. Methods: An observational retrospective analysis of 1861 patients, with SARS-CoV-2 confirmed by RT-qPCR, from 10 hospitals across Europe was performed. Biomarkers, taken upon presentation to Emergency Departments (ED), clinical scores, patient demographics and outcomes were collected. Multiclass random forest classifier models were generated as well as calculation of area under the curve analysis. The primary endpoint was hospital admission with and without death. Results: Patients suitable for safe discharge from Emergency Departments could be identified through an MR-proADM value of ≤ 1.02&nbsp;nmol/L in combination with a CRP (C-Reactive Protein) of ≤ 20.2&nbsp;mg/L and age ≤ 64, or in combination with a SOFA (Sequential Organ Failure Assessment) score &lt; 2 if MR-proADM was ≤ 0.83&nbsp;nmol/L regardless of age. Those at an increased risk of mortality could be identified upon presentation to secondary care with an MR-proADM value of &gt; 0.85&nbsp;nmol/L, in combination with a SOFA score ≥ 2 and LDH &gt; 720 U/L, or in combination with a CRP &gt; 29.26&nbsp;mg/L and age ≤ 64, when MR-proADM was &gt; 1.02&nbsp;nmol/L. Conclusions: This international study suggests that for patients presenting to the ED with confirmed SARS-CoV-2 infection, MR-proADM in combination with age and CRP or with the patient’s SOFA score could identify patients at low risk where outpatient treatment may be safe