Optimized molecular resolution of cross-contamination alerts in clinical mycobacteriology laboratories

<p>Abstract</p> <p>Background</p> <p>The phenomenon of misdiagnosing tuberculosis (TB) by laboratory cross-contamination when culturing <it>Mycobacterium tuberculosis </it>(MTB) has been widely reported and it has an obvious clinical, therapeutic and social impact. The final confirmation of a cross-contamination event requires the molecular identification of the same MTB strain cultured from both the potential source of the contamination and from the false-positive candidate. The molecular tool usually applied in this context is IS6110-RFLP which takes a long time to provide an answer, usually longer than is acceptable for microbiologists and clinicians to make decisions. Our purpose in this study is to evaluate a novel PCR-based method, MIRU-VNTR as an alternative to assure a rapid and optimized analysis of cross-contamination alerts.</p> <p>Results</p> <p>MIRU-VNTR was prospectively compared with IS6110-RFLP for clarifying 19 alerts of false positivity from other laboratories. MIRU-VNTR highly correlated with IS6110-RFLP, reduced the response time by 27 days and clarified six alerts unresolved by RFLP. Additionally, MIRU-VNTR revealed complex situations such as contamination events involving polyclonal isolates and a false-positive case due to the simultaneous cross-contamination from two independent sources.</p> <p>Conclusion</p> <p>Unlike standard RFLP-based genotyping, MIRU-VNTR i) could help reduce the impact of a false positive diagnosis of TB, ii) increased the number of events that could be solved and iii) revealed the complexity of some cross-contamination events that could not be dissected by IS6110-RFLP.</p

Factors associated with non-participation in and dropout from cardiac rehabilitation programmes: a systematic review of prospective cohort studies

Background: Although evidence exists for the efficacy of cardiac rehabilitation programmes to reduce morbidity and mortality among patients with cardiovascular disease, cardiac rehabilitation programmes are underused. We aimed systematically to review the evidence from prospective cohort studies on factors associated with non-participation in and/or dropping out from cardiac rehabilitation programmes. Methods: MedLine, Embase, Scopus, Open Grey and Cochrane Database were searched for relevant publications from inception to February 2018. Search terms included (a) coronary heart disease and other cardiac conditions; (b) cardiac rehabilitation and secondary prevention; and (c) non-participation in and/or dropout. Databases were searched following the PRISMA statement. Study selection, data extraction and the assessment of study quality were performed in duplicate. Results: We selected 43 studies with a total of 63,425 patients from 10 different countries that met the inclusion criteria. Factors associated with non-participation in and dropout from cardiac rehabilitation were grouped into six broad categories: intrapersonal factors, clinical factors, interpersonal factors, logistical factors, cardiac rehabilitation programme factors and health system factors. We found that clinical factors, logistical factors and health system factors were the main factors assessed for non-participation in cardiac rehabilitation. We also found differences between the factors associated with non-participation and dropout. Conclusions: Several factors were determinant for non-participation in and dropout from cardiac rehabilitation. These findings could be useful to clinicians and policymakers for developing interventions aimed at improving participation and completion of cardiac rehabilitation, such as E-health or home-based delivery programmes. Trial Registration: International Prospective Register of Systematic Reviews (PROSPERO) identifier: CRD42016032973

The Allium Derivate Propyl Propane Thiosulfinate Exerts Anti-Obesogenic Effects in a Murine Model of Diet-Induced Obesity

This study is supported by the Spanish Ministry of Science and Innovation (MICINN) (grants PID2020-119536RB-I00 and CIEN IDI-20170847). The FPU contract to R.L.-G. from Spanish Ministry of Universities (FPU 18/02026) and the contract Juan de la Cierva-Incorporacion (IJCI-2017-32485) to MO are fully acknowledge.Allium species and their organosulfur-derived compounds could prevent obesity and metabolic dysfunction, as they exhibit immunomodulatory and antimicrobial properties. Here, we report the anti-obesogenic potential and dose-dependent effects (0.1 or 1 mg/kg/day) of propyl propane thiosulfinate (PTS) in a murine model of diet-induced obesity. The obesogenic diet increased body weight gain and adipocyte size, and boosted inflammatory marker (Cd11c) expression in the adipose tissue. Conversely, PTS prevented these effects in a dose-dependent manner. Moreover, the higher dose of PTS improved glucose and hepatic homeostasis, modulated lipid metabolism, and raised markers of the thermogenic capacity of brown adipose tissue. In the colon, the obesogenic diet reduced IL-22 levels and increased gut barrier function markers (Cldn3, Muc2, Reg3g, DefaA); however, the highest PTS dose normalized all of these markers to the levels of mice fed a standard diet. Gut microbiota analyses revealed no differences in diversity indexes and only minor taxonomic changes, such as an increase in butyrate producers, Intestimonas and Alistipes, and a decrease in Bifidobacterium in mice receiving the highest PTS dose. In summary, our study provides preclinical evidence for the protective effects of PTS against obesity, which if confirmed in humans, might provide a novel plant-based dietary product to counteract this condition.Spanish GovernmentEuropean Commission PID2020-119536RB-I00 CIEN IDI-20170847Spanish Government FPU 18/02026contract Juan de la Cierva-Incorporacion IJCI-2017-3248

MicroRNA-661 modulates redox and metabolic homeostasis in colon cancer

Cancer cell survival and metastasis are dependent on metabolic reprogramming that is capable of increasing resistance to oxidative and energetic stress. Targeting these two processes can be crucial for cancer progression. Herein, we describe the role of microRNA-661 (miR661) as epigenetic regulator of colon cancer (CC) cell metabolism. MicroR661 induces a global increase in reactive oxygen species, specifically in mitochondrial superoxide anions, which appears to be mediated by decreased carbohydrate metabolism and pentose phosphate pathway, and by a higher dependency on mitochondrial respiration. MicroR661 overexpression in non-metastatic human CC cells induces an epithelial-to-mesenchymal transition phenotype, and a reduced tolerance to metabolic stress. This seems to be a general effect of miR661 in CC, since metastatic CC cell metabolism is also compromised upon miR661 overexpression. We propose hexose-6-phosphate dehydrogenase and pyruvate kinase M2 as two key players related to the observed metabolic reprogramming. Finally, the clinical relevance of miR661 expression levels in stage-II and III CC patients is discussed. In conclusion, we propose miR661 as a potential modulator of redox and metabolic homeostasis in CC.This work was supported by Ministerio de Econom ıa y Competitividad del Gobierno de España (MINECO/FEDER Plan Nacional I+D+i AGL201348943-C2 and AGL2016-76736-C3-3-R), Gobierno regional de la Comunidad de Madrid (P2013/ABI2728, ALIBIRD-CM) and EU Structural Funds.S

Small Molecules as Dream Modulators: New Avenues for the Search of Drugs for Neurodegenerative Diseases

Trabajo presentado en el 9th drug Design and Medicinal Chemistry, celebrado en Berlín (Alemania) del 05 al 06 de mayo de 2015.Altered neuronal calcium homeostasis and early compensatory changes in transcriptional programs are common features of many neurodegenerative pathologies including Alzheimer¿s disease, Down syndrome and Huntington¿s disease. DREAM (Downstream Regulatory Element Antagonist Modulator), also known as calsenilin or KChIP-3 (potassium channel interacting protein-3), is a multifunctional calcium binding protein that controls the expression level and/or the activity of several proteins related to calcium homeostasis, neuronal excitability and neuronal survival. This protein is widely expressed in the brain and, depending on the cell type and physiological conditions, shows multiple subcellular localizations, in the nucleus, cytosol or cell membrane. The interest in DREAM is based on its key role in the regulation of intracellular calcium levels. As a calcium-dependent transcriptional repressor, DREAM is a master regulator of activity-dependent gene expression and controls genes important for calcium homeostasis such as the sodium/calcium exchanger-3 (NCX3), IP3R and L-type calcium channels. As an auxiliary protein in the plasma membrane, DREAM interacts with and regulates the gating of Kv4 potassium channels, L- and T-type voltage-dependent calcium channels and NMDA receptors. These findings suggest that DREAM could be a novel and versatile target for therapeutic intervention in neurodegeneration and that molecules able to bind to DREAM and block its physiological functions could be candidates for drugs to treat neurodegenerative diseases. Moreover, up to now, only two DREAM-binding molecules have been identified. In this communication we report the rational design and the synthesis of novel DREAM-binding molecules and their effects on the modulation of DREAM/protein interactions

Tiempo de setas: estudiando la influencia del cambio climático en los hongos del Parque Nacional de Ordesa y Monte Perdido

Proyecto «Tiempo de Setas: El impacto del cambio climático en las comunidades de hongos del suelo en Parques Nacionales de montaña» (2711/2021), financiado por el Organismo Autónomo de Parques Nacionales y el Ministerio de Innovación y Ciencia

Synthesis, conformational analysis, and cytotoxicity of conformationally constrained aplidine and tamandarin A analogues incorporating a spirolactam β-turn mimetic

With the aim of studying the contribution of the β II turn conformation at the side chain of didemnins to the bioactive conformation responsible for their antitumoral activity, conformationally restricted analogues of aplidine and tamandarin A, where the side chain dipeptide Pro8-N-Me-d-Leu7 is replaced with the spirolactam β II turn mimetic (5R)-7-[(1R)-1-carbonyl-3-methylbutyl]-6-oxo-1,7-diazaspiro[4.4]nonane, were prepared. Additionally, restricted analogues, where the aplidine (pyruvyl9) or tamandarin A [(S)-Lac9] acyl groups are replaced with the isobutyryl, Boc, and 2-methylacryloyl groups, were also prepared. These structural modifications were detrimental to cytotoxic activity, leading to a decrease of 1−2 orders of magnitude with respect to that exhibited by aplidine and tamandarin A. The conformational analysis of one of these spirolactam aplidine analogues, by NMR and molecular modeling methods, showed that the conformational restriction caused by the spirolactam does not produce significant changes in the overall conformation of aplidine, apart from preferentially stabilizing the trans rotamer at the pyruvyl9−spirolactam amide bond, whereas in aplidine both cis and trans rotamers at the pyruvyl9−Pro8 amide bond are more or less equally stabilized. These results seem to indicate a preference for the cis form at that amide bond in the bioactive conformation of aplidine. The significant influence of this cis/trans isomerism upon the cytotoxicity suggests a possible participation of a peptidylprolyl cis/trans isomerase in the mechanism of action of aplidine.This work was supported by CICYT (Grant SAF2000-0147), MCYT-FEDER (Grant BIO2002-2301), Generalitat de Catalunya (Group Consolidat 1999SGR0042 and Centre de Referència en Biotecnologia), and Pharma Mar, S.A

Eating disorders during gestation: Implications for mother's health, fetal outcomes, and epigenetic changes

Introduction: Eating disorders (EDs) have increased globally in women of childbearing age, related to the concern for body shape promoted in industrialized countries. Pregnancy may exacerbate a previous ED or conversely may be a chance for improving eating patterns due to the mother's concern for the unborn baby. EDs may impact pregnancy evolution and increase the risk of adverse outcomes such as miscarriage, preterm delivery, poor fetal growth, or malformations, but the knowledge on this topic is limited. Methods: We performed a systematic review of studies on humans in order to clarify the mechanisms underpinning the adverse pregnancy outcomes in patients with EDs. Results: Although unfavorable fetal development could be multifactorial, maternal malnutrition, altered hormonal pathways, low pre-pregnancy body mass index, and poor gestational weight gain, combined with maternal psychopathology and stress, may impair the evolution of pregnancy. Environmental factors such as malnutrition or substance of abuse may also induce epigenetic changes in the fetal epigenome, which mark lifelong health concerns in offspring. Conclusions: The precocious detection of dysfunctional eating behaviors in the pre-pregnancy period and an early multidisciplinary approach comprised of nutritional support, psychotherapeutic techniques, and the use of psychotropics if necessary, would prevent lifelong morbidity for both mother and fetus. Further prospective studies with large sample sizes are needed in order to design a structured intervention during every stage of pregnancy and in the postpartum period

Interobserver and Intertest Agreement in Telemedicine Glaucoma Screening with Optic Disk Photos and Optical Coherence Tomography

t: Purpose: To evaluate interobserver and intertest agreement between optical coherence tomography (OCT) and retinography in the detection of glaucoma through a telemedicine program. Methods: A stratified sample of 4113 individuals was randomly selected, and those who accepted underwent examination including visual acuity, intraocular pressure (IOP), non-mydriatic retinography, and imaging using a portable OCT device. Participants' data and images were uploaded and assessed by 16 ophthalmologists on a deferred basis. Two independent evaluations were performed for all participants. Agreement between methods was assessed using the kappa coefficient and the prevalence-adjusted bias-adjusted kappa (PABAK). We analyzed potential factors possibly influencing the level of agreement. Results: The final sample comprised 1006 participants. Of all suspected glaucoma cases (n = 201), 20.4% were identified in retinographs only, 11.9% in OCT images only, 46.3% in both, and 21.4% were diagnosed based on other data. Overall interobserver agreement outcomes were moderate to good with a kappa coefficient of 0.37 and a PABAK index of 0.58. Higher values were obtained by experienced evaluators (kappa = 0.61; PABAK = 0.82). Kappa and PABAK values between OCT and photographs were 0.52 and 0.82 for the first evaluation. Conclusion: In a telemedicine screening setting, interobserver agreement on diagnosis was moderate but improved with greater evaluator expertise

Legal and Forensic Medicine Specialty in Spain: the consolidation by the medical residency system

The specialty of Legal and Forensic Medicine (Medicina Legal y Forense [MLF]) emerged through the need for doctors to serve the Justice Administration as advisors to the Courts and Tribunals in the resolution of medical/biological issues arising in the field of law enforcement, establishing a bridge between medicine and law. MLF started in 1843 when Pere Mata's plan to reform the teaching of Medicine at Spanish universities included MLF as an individual discipline in the studies of Medicine and Surgery, and the first MLF chair was created at the Universidad Central of Madrid. Later, in 1855, the role of the forensic doctor was established with the enactment of the Health Law, which led to the creation of the Corps of Forensic Doctors (Cuerpo de Médicos Forenses [CMF]) in 1862.1 Since then, academic legal medicine and the professional legal medicine practiced by the forensic doctors of the Justice Administration have become somewhat separated. On the one hand, academic MLF, under the university faculty, has been primarily concerned with the provision of undergraduate teaching, as well as MLF research and knowledge transfer. On the other hand, the practical aspects involved in assisting the Justice Administration has fallen in the main to professional MLF