Human exceptional longevity: transcriptome from centenarians is distinct from septuagenarians and reveals a role of Bcl-xL in successful aging

24 páginas, 7 figuras. Borras C, et al. Human exceptional longevity: transcriptome from centenarians is distinct from septuagenarians and reveals a role of Bcl-xL in successful aging. Aging (Albany NY). 2016 Oct 28;8(12):3185-3208. doi: 10.18632/aging.101078.Centenarians not only enjoy an extraordinary aging, but also show a compression of morbidity. Using functional transcriptomic analysis of peripheral blood mononuclear cells (PMBC) we identified 1721 mRNAs differentially expressed by centenarians when compared with septuagenarians and young people. Sub-network analysis led us to identify Bcl-xL as an important gene up-regulated in centenarians. It is involved in the control of apoptosis, cellular damage protection and also in modulation of immune response, all associated to healthy aging. Indeed, centenarians display lower plasma cytochrome C levels, higher mitochondrial membrane potential and also less cellular damage accumulation than septuagenarians. Leukocyte chemotaxis and NK cell activity are significantly impaired in septuagenarians compared with young people whereas centenarians maintain them. To further ascertain the functional role of Bcl-xL in cellular aging, we found that lymphocytes from septuagenarians transduced with Bcl-xL display a reduction in senescent-related markers. Finally, to demonstrate the role of Bcl-xL in longevity at the organism level, C. elegans bearing a gain of function mutation in the Bcl-xL ortholog ced-9, showed a significant increase in mean and maximal life span. These results show that mRNA expression in centenarians is unique and reveals that Bcl-xL plays an important role in exceptional aging.This work was supported by grants SAF2013-44663-R, from the Spanish Ministry of Education and Science (MEC); ISCIII2012-RED-43-029 from the “Red Tematica de investigacion cooperative en envejecimiento y fragilidad” (RETICEF); PROMETEOII/2014/056 from "Conselleria d’Educació, Cultura I Esport de la Generalitat Valenciana"; and EU Funded CM1001 and FRAILOMIC-HEALTH.2012.2.1.1-2 (To J.V) APM-03/15 from Conselleria de Sanitat, AICO/2016/067 and from Conselleria d’Educació, Cultura i Esport de la Generalitat Valenciana, Intramural Grant from INCLIVA (to C.B.),VAL i+d Fellowship from Generalitat Valenciana (to C.L.-F.) and Marie Curie Career Integration Grant (to N.F). This study has been co-financed by FEDER funds from the European Union.Peer reviewe

Porous Poly(3,4-ethylenedioxythiophene)-Based Electrodesfor Detecting Stress Biomarkers in Artificial Urine and Sweat

When danger is perceived, the human body responds to overcome obstacles and survive a stressful situation; however, sustained levels of stress are associated with health disorders and diminished life quality. Hence, stress biomarkers are monitored to control stress quantitatively. Herein, a porous sensor (4l-COP/p) composed of poly(3,4-ethylenedioxythiophene) (PEDOT) and poly(3,4-ethylenedioxythiophene-co-N-methylpyrrole) (COP), which is prepared in a four-layered fashion to detect dopamine (DA) and serotonin (5-HT), is presented. Specifically, the detection is conducted in phosphate-buffered saline (PBS), as well as artificial urine and sweat, by applying cyclic voltammetry. The limit of detection values obtained are as low as 5.7 × 10−6 and 1.4 × 10−6 m for DA and 5-HT, respectively, when assessed individually in artificial urine. When mixed in PBS, 4l-COP/p detects both biomarkers with a resolution of 0.18 V and a sensitivity of 40 and 30 μA mm−1 for DA and 5-HT, respectively. Additionally, by theoretical calculations, the interaction pattern that each stress biomarker establishes with the PEDOT outer layer is elucidated. Whereas DA interacts with the ������-system of PEDOT, 5-HT forms specific hydrogen bonds with the conducting polymer chains. The resolution value obtained depends upon such interactions. Overall, 4l-COP/p electrodes display potential as stress sensing devices for healthcare technologies.Authors acknowledge MINECO/FEDER (RTI2018-098951-B-I00), the Agència de Gestió d'Ajuts Universitaris i de Recerca (2017SGR359). M.M.P.-M. thanks the Spanish Ministry of Educación y Formación Profesional for the Junior Beatriz Galindo Award (BG20/00216)

Consensus of Spanish Society of Hospital Pharmacy on optimal medication therapy management of atopic dermatitis.

Atopic Dermatitis; Hospital Pharmacy; Multidisciplinary approachDermatitis atòpica; Farmàcia hospitalària; Enfocament multidisciplinariDermatitis atópica; Farmacia hospitalaria; Enfoque multidisciplinarioAim: This study's aims are: 1) To use the Delphi method to determine the level of consensus among hospital pharmacists (HPs) as regards the factors involved in the current approach to patients with atopic dermatitis (AD); 2) To identify potential areas for improvement in hospital pharmacy in terms of dealing with patients with severe AD; and 3) To contribute to adequate pharmaceutical care for patients with AD by drawing up recommendations. Methods: A two-round Delphi survey with participation from HPs from all over Spain. Three theme-based blocks were set out: 1) AD; 2) Management of patients with severe AD in the Hospital Pharmacy setting; and 3) Unmet needs (pathology, patient, treatment and management). Results: The 42 HPs participating reached a consensus in recognising the impact of severe AD on the patients suffering from it, the need to encourage adherence and the recommendations to use scales that take into account the patient's quality of life and indicators of the patient's experience. It has also been demonstrated that it is worthwhile evaluating the results in real clinical practice in consensus with other specialists from the multidisciplinary team. Finally, it is advisable to use drugs that have demonstrated long-term effectiveness and safety for patients with severe AD, given the disease's chronic nature. Conclusions: This Delphi consensus highlights the impact of severe AD on patients, the importance of a multidisciplinary and holistic approach, in which HP play a major role. It also highlights the importance of increased access to new drugs to improve health outcomes

The impact of immigration and vaccination in reducing the incidence of hepatitis B in Catalonia (Spain)

Background The Hepatitis B virus (HBV) infection is a major cause of liver disease and liver cancer worldwide according to the World Health Organization. Following acute HBV infection, 1-5% of infected healthy adults and up to 90% of infected infants become chronic carriers and have an increased risk of cirrhosis and primary hepatocellular carcinoma. The aim of this study was to investigate the relationship between the reduction in acute hepatitis B incidence and the universal vaccination programme in preadolescents in Catalonia (Spain), taking population changes into account, and to construct a model to forecast the future incidence of cases that permits the best preventive strategy to be adopted. Methods Reported acute hepatitis B incidence in Catalonia according to age, gender, vaccination coverage, percentage of immigrants and the year of report of cases was analysed. A statistical analysis was made using three models: generalized linear models (GLM) with Poisson or negative binomial distribution and a generalized additive model (GAM). Results The higher the vaccination coverage, the lower the reported incidence of hepatitis B (p  70%, the reduction in incidence was 2-fold higher than in groups with a coverage <70% (p <0.01). The increase in incidence was significantly-higher in groups with a high percentage of immigrants and more than 15% (p <0.01) in immigrant males of working age (19-49 years). Conclusions The results of the adjusted models in this study confirm that the global incidence of hepatitis B has declined in Catalonia after the introduction of the universal preadolescent vaccination programme, but the incidence increased in male immigrants of working age. Given the potential severity of hepatitis B for the health of individuals and for the community, universal vaccination programmes should continue and programmes in risk groups, especially immigrants, should be strengthened.Postprint (published version

High Fundamental Frequency Quartz Crystal Microbalance (HFF-QCMD) Immunosensor for detection of sulfathiazole in honey

[EN] In this study, a piezoelectric immunosensor based on High Fundamental Frequency Quartz Crystal Microbalance (HFF-QCMD) technology was developed for detection of sulfathiazole in honey. The biorecognition was based on a competitive immunoassay in the conjugate-coated format, using monoclonal antibodies as specific im-munoreagents. The quantification of sulfathiazole was performed by building the corresponding calibration standard curve in diluted honey (1/140). Due to the competitive nature of the immunoassay, the standard curve showed a sigmoidal pattern with limits of detection (LOD) and quantification (LOQ) of 0.10 ¿g/kg and 2 ¿g/kg honey, respectively. The LOD reached by this immunosensor is 40¿50 times lower than those reported by other techniques for antibiotic detection. Moreover, this method requires minimum honey pre-treatment, making it faster and simpler than other methods. This immunosensor meets the precision and accuracy requirements established by SANCO guidelines, when sulfathiazole concentration in honey is not lower than 10 ¿g/kg. These findings could be the basis for reaching enough reliability for lower concentrations. Therefore, HFF-QCMD immunosensors can be considered a feasible alternative to current techniques for rapid and highly sensitive determination of sulfathiazole in honey with minimum sample preparation.The Spanish Ministry of Economy and Competitiveness, with FEDER-funds, has financially supported this work through the AGL 2013-48646-R project. Furthermore, authors are grateful for financial support from the European Social Fund and the Generalitat Valenciana for the PhD grant (Ayudas para la contratación de personal investigador en formación de carácter predoctoral) to Lourdes Cervera Chiner (ACIF/2016/132). The authors would also like to thank the Universitat Politècnica de València for the support provided for contracting Marisol Juan Borrás in the frame of PAID-10-17 (Ayuda para la contratación de acceso al Sistema Español de Ciencia, Tecnología e Innovación en Estructuras de Investigación).Cervera-Chiner, L.; Jiménez Jiménez, Y.; Montoya, Á.; Juan-Borras, MDS.; Pascual, N.; Arnau Vives, A.; Escriche Roberto, MI. (2020). High Fundamental Frequency Quartz Crystal Microbalance (HFF-QCMD) Immunosensor for detection of sulfathiazole in honey. Food Control. 115:1-6. https://doi.org/10.1016/j.foodcont.2020.107296S1611

Effect of sludge age on the consortium of microorganisms microbial consortia developed in MFCs

BACKGROUND: This work is focused on the assessment of the performance of mini-scale air-breathing microbial fuel cells (MFCs),by monitoring the evolution of the bio-electrogenic activity for a period of 40 days and by comparing the microorganismspopulations developed in each of the MFCs after this period.RESULTS: Five MFCs were operated at sludge ages ranging from 1.4 to 10.0 days. Results showed the superb performance of theMFC operating under a sludge age of 2.5 days. Desulfuromonas, Syntrophothermus, Solitalea, Acholeplasma, Propionicimonas,Desulfobacula and Sphaerochaeta are proposed as potentially responsible for the bio-electrogenic activity.CONCLUSIONS: Microbial population analysis through Illumina amplicon sequencing demonstrated that despite all MFCsbeing seeded with the same mixed culture inoculum, the biological cultures developed in the suspension and the biofilm arecompletely different and depend strongly on sludge age.© 2017 Society of Chemical Industry

Human exceptional longevity: transcriptome from centenarians is distinct from septuagenarians and reveals a role of Bcl‐xL in successful aging

Centenarians not only enjoy an extraordinary aging, but also show a compression of morbidity. Using functional transcriptomic analysis of peripheral blood mononuclear cells (PMBC) we identified 1721 mRNAs differentially expressed by centenarians when compared with septuagenarians and young people. Sub‐network analysis led us to identify Bcl ‐ xL as an important gene up‐regulated in centenarians. It is involved in the control of apoptosis, cellular damage protection and also in modulation of immune response, all associated to healthy aging. Indeed, centenarians display lower plasma cytochrome C levels, higher mitochondrial membrane potential and also less cellular damage accumulation than septuagenarians. Leukocyte chemotaxis and NK cell activity are significantly impaired in septuagenarians compared with young people whereas centenarians maintain them. To further ascertain the functional role of Bcl‐ xL in cellular aging, we found that lymphocytes from septuagenarians transduced with Bcl‐xL display a reduction in senescent‐related markers. Finally, to demonstrate the role of BcL‐xL in longevity at the organism level, C. elegans bearing a gain of function mutation in the BcL‐xL ortholog ced‐9, showed a significant increase in mean and maximal life span. These results show that mRNA expression in centenarians is unique and reveals that BcL‐ xL plays an important role in exceptional aging

Cognitive reserve and its correlates in child and adolescent offspring of patients diagnosed with schizophrenia or bipolar disorder

Aim: To analyze cognitive reserve (CR) in child and adolescent offspring of patients diagnosed with schizophrenia (SZ-off) or bipolar disorder (BD-off) and compare them with a group of community controls (CC-off). We also aimed to investigate whether there was an association between CR and clinical and neuropsychological variables according to group. Methods: The study included 46 SZ-off, 105 BD-off and 102 CC-off. All participants completed assessments regarding CR and clinical, neuropsychological and psychosocial functioning. CR was measured with a proxy based on premorbid intelligence, parental occupational level, educational attainment, developmental milestones and sociability. The clinical assessment included the Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime, the Semi-structured Interview for Prodromal Syndromes, and the Global Assessment Functioning scale. The neuropsychological assessment included measures of executive functioning, attention, verbal memory, working memory and processing speed. Results: SZ-off showed a lower level of CR compared to BD-off and CC-off, while BD-off showed an intermediate level of CR between SZ-off and CC-off. Moreover, an association between higher CR and less lifetime psychopathology, fewer prodromal psychotic symptoms, higher psychosocial functioning, and a higher working memory score was observed in all groups, but it was stronger in SZ-off. Conclusions: CR seemed to be associated with psychopathology, clinical symptoms, psychosocial functioning, and some cognitive functions. SZ-off appeared to benefit more from a higher CR, therefore it could be considered a protective factor against the development of clinical symptomatology and cognitive impairment