987 research outputs found
Using bacterial biomarkers to identify early indicators of cystic fibrosis pulmonary exacerbation onset
No full textAcute periods of pulmonary exacerbation are the single most important cause of morbidity in cystic fibrosis patients, and may be associated with a loss of lung function. Intervening prior to the onset of a substantially increased inflammatory response may limit the associated damage to the airways. While a number of biomarker assays based on inflammatory markers have been developed, providing useful and important measures of disease during these periods, such factors are typically only elevated once the process of exacerbation has been initiated. Identifying biomarkers that can predict the onset of pulmonary exacerbation at an early stage would provide an opportunity to intervene before the establishment of a substantial immune response, with major implications for the advancement of cystic fibrosis care. The precise triggers of pulmonary exacerbation remain to be determined; however, the majority of models relate to the activity of microbes present in the patient's lower airways of cystic fibrosis. Advances in diagnostic microbiology now allow for the examination of these complex systems at a level likely to identify factors on which biomarker assays can be based. In this article, we discuss key considerations in the design and testing of assays that could predict pulmonary exacerbations
Endometriosis: alternative methods of medical treatment
No full textLeticia Muñoz-Hernando,1 Jose L Muñoz-Gonzalez,1 Laura Marqueta-Marques,1 Carmen Alvarez-Conejo,1 Álvaro Tejerizo-García,1 Gregorio Lopez-Gonzalez,1 Emilia Villegas-Muñoz,2 Angel Martin-Jimenez,3 Jesús S Jiménez-López1 1Endometriosis Unit, Service of Obstetrics and Gynecology, Hospital Universitario 12 de Octubre, Madrid, Spain; 2Endometriosis Unit, Service of Obstetrics and Gynecology, Hospital Carlos Haya, Malaga, Spain; 3Endometriosis Unit, Service of Obstetrics and Gynecology, Hospital Son Llatzer, Palma de Mallorca, Spain Abstract: Endometriosis is an inflammatory estrogen-dependent disease defined by the presence of endometrial glands and stroma at extrauterine sites. The main purpose of endometriosis management is alleviating pain associated to the disease. This can be achieved surgically or medically, although in most women a combination of both treatments is required. Long-term medical treatment is usually needed in most women. Unfortunately, in most cases, pain symptoms recur between 6 months and 12 months once treatment is stopped. The authors conducted a literature search for English original articles, related to new medical treatments of endometriosis in humans, including articles published in PubMed, Medline, and the Cochrane Library. Keywords included “endometriosis” matched with “medical treatment”, “new treatment”, “GnRH antagonists”, “Aromatase inhibitors”, “selective progesterone receptor modulators”, “anti-TNF α”, and “antiangiogenic factors”. Hormonal treatments currently available are effective in the relief of pain associated to endometriosis. Among new hormonal drugs, association to aromatase inhibitors could be effective in the treatment of women who do not respond to conventional therapies. GnRh antagonists are expected to be as effective as GnRH agonists, but with easier administration (oral). There is a need to find effective treatments that do not block the ovarian function. For this purpose, antiangiogenic factors could be important components of endometriosis therapy in the future. Upcoming researches and controlled clinical trials should focus on these drugs. Keywords: pharmacological treatment options, aromatase inhibitors, GnRH antagonists, selective progesterone receptor modulators, anti-TNF-α, endometrial tissue, antiangiogenic factors, hormonal treatment
Measurement of enthalpies of vaporization of volatile heterocyclic compounds by DSC
No full textOBJECTIVE: The aim of this study was to review clinical data and outcomes of patients with burns in a Mexican non-burn intensive care unit (ICU). METHODS: We did a retrospective analysis of our single-centre database of burn patients admitted to the ICU in the Hospital Civil Fray Antonio Alcalde (University Hospital). The sample was divided for analysis into two groups according to the outcome 'death' or 'discharge' from ICU. RESULTS: Overall mortality was 58.2%, without a decreasing trend in mortality rates through the years. We identified the presence of third-degree burns (odds ratio (OR) 1.5, p=0.003), and >49% total burned surface area (TBSA; OR 3.3, p<0.001) was associated with mortality. Mean age was higher in deceased patients (38.2 years vs. 31.3 years, p=0.003) as was the TBSA (62.8% vs. 36.4%, p<0.001). At multivariate analysis, inhalation injury was not associated with increased mortality, but it was with more mechanical ventilation days. Early surgical debridement/cleansing was performed in most patients; however, the mean of the procedures was 1.7 per patient in both groups. CONCLUSION: We identified significant factors associated with mortality. These variables and prognosis from non-burn ICUs differ broadly compared with burn intensive care units (BICUs); thus, more structured, multidisciplinary and specialised treatment strategies are still needed.Copyright ?" 2014 Elsevier Ltd and ISBI. All rights reserved.",,"Record Owner: From MEDLINE, a database of the U.S. National Library of Medicine.; Status: MEDLINE; Publishing Model: Journal available in: Print-Electronic Citation processed from: Internet; NLM Journal Code: afc, 8913178; Keyword Heading: Major burn Mortality Non-burn ICU Prognosis; Publisher Item Identifier: S0305-4179(14)00004-7; Entry Date: 20150511",,,,"10.1016/j.burns.2013.12.020",,"1879-1409; 0305-4179","http://hdl.handle.net/20.500.12104/37352","http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=24560957",,"English",,,,"6",,"Burns",,"122
AlloViz: A tool for the calculation and visualisation of protein allosteric communication networks
No full textAllostery, the presence of functional interactions between distant parts of proteins, is a critical concept in the field of biochemistry and molecular biology, particularly in the context of protein function and regulation. Understanding the principles of allosteric regulation is essential for advancing our knowledge of biology and developing new therapeutic strategies. This paper presents AlloViz, an open-source Python package designed to quantitatively determine, analyse, and visually represent allosteric communication networks on the basis of molecular dynamics (MD) simulation data. The software integrates well-known techniques for understanding allosteric properties simplifying the process of accessing, rationalising, and representing protein allostery and communication routes. It overcomes the inefficiency of having multiple methods with heterogeneous implementations and showcases the advantages of using MD simulations and multiple replicas to obtain statistically sound information on protein dynamics; it also enables the calculation of "consensus-like" scores aggregating methods that consider multiple structural aspects of allosteric networks. We demonstrate the features of AlloViz on two proteins: β-arrestin 1, a key player for regulating G protein-coupled receptor (GPCR) signalling, and the protein tyrosine phosphatase 1B, an important pharmaceutical target for allosteric inhibitors. The software includes comprehensive documentation and examples, tutorials, and a user-friendly graphical interface.DAG acknowledges financial support from the Catalan Department of Business and Innovation [2020FISDU/487]. TG acknowledges funding from the Spoke 7 of the National Centre for HPC, Big Data and Quantum Computing [CN00000013, CUP B93C22000620006] and from PRIN 2022 [BioCat4BioPol, CUP B53D23015140006] from the Ministero dell'Università e Ricerca, funded by the European Union – NextGenerationEU. JS acknowledges funding from MICIU/AEI/10.13039/501100011033 and the ERDF/EU (grant number PID2022-137161OB-I00). JS acknowledges further funding from the Horizon Europe Project OBELISK under the grant agreement 101080465. JS has been financially supported by the Instituto de Salud Carlos III FEDER [PI18/00094] and the ERA-NET NEURON & Ministry of Economy, Industry, and Competitiveness [AC18/00030]. Funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the European Health and Digital Executive Agency (HADEA). Neither the European Union nor the granting authority can be held responsible for them. We acknowledge the CINECA awards under the ISCRA initiative for the availability of high performance computing resources and support. FNF, AMP, MLB, DAG, TG and JS have been members of COST Action CA18133 “ERNEST”
Pharmacogenetics of ophthalmic topical β-blockers
No full textGlaucoma is the second leading cause of blindness worldwide. The primary glaucoma risk factor is elevated intraocular pressure. Topical β-blockers are affordable and widely used to lower intraocular pressure. Genetic variability has been postulated to contribute to interpersonal differences in efficacy and safety of topical β-blockers. This review summarizes clinically significant polymorphisms that have been identified in the β-adrenergic receptors (ADRB1, ADRB2 and ADRB3). The implications of polymorphisms in CYP2D6 are also discussed. Although the candidate-gene approach has facilitated significant progress in our understanding of the genetic basis of glaucoma treatment response, most drug responses involve a large number of genes, each containing multiple polymorphisms. Genome-wide association studies may yield a more comprehensive set of polymorphisms associated with glaucoma outcomes. An understanding of the genetic mechanisms associated with variability in individual responses to topical β-blockers may advance individualized treatment at a lower cost
North American import? Charting the origins of an enigmatic Trypanosoma cruzi domestic genotype.
No full textBACKGROUND: Trypanosoma cruzi, the agent of Chagas disease, is currently recognized as a complex of six lineages or Discrete Typing Units (DTU): TcI-TcVI. Recent studies have identified a divergent group within TcI - TcI(DOM). TcI(DOM). is associated with a significant proportion of human TcI infections in South America, largely absent from local wild mammals and vectors, yet closely related to sylvatic strains in North/Central America. Our aim was to examine hypotheses describing the origin of the TcI(DOM) genotype. We propose two possible scenarios: an emergence of TcI(DOM) in northern South America as a sister group of North American strain progenitors and dispersal among domestic transmission cycles, or an origin in North America, prior to dispersal back into South American domestic cycles. To provide further insight we undertook high resolution nuclear and mitochondrial genotyping of multiple Central American strains (from areas of México and Guatemala) and included them in an analysis with other published data. FINDINGS: Mitochondrial sequence and nuclear microsatellite data revealed a cline in genetic diversity across isolates grouped into three populations: South America, North/Central America and TcI(DOM). As such, greatest diversity was observed in South America (A(r) = 4.851, π = 0.00712) and lowest in TcI(DOM) (Ar = 1.813, π = 0.00071). Nuclear genetic clustering (genetic distance based) analyses suggest that TcI(DOM) is nested within the North/Central American clade. CONCLUSIONS: Declining genetic diversity across the populations, and corresponding hierarchical clustering suggest that emergence of this important human genotype most likely occurred in North/Central America before moving southwards. These data are consistent with early patterns of human dispersal into South America
Differential response of skeletal muscles to mTORC1 signaling during atrophy and hypertrophy
No full textBACKGROUND: Skeletal muscle mass is determined by the balance between protein synthesis and degradation. Mammalian target of rapamycin complex 1 (mTORC1) is a master regulator of protein translation and has been implicated in the control of muscle mass. Inactivation of mTORC1 by skeletal muscle-specific deletion of its obligatory component raptor results in smaller muscles and a lethal dystrophy. Moreover, raptor-deficient muscles are less oxidative through changes in the expression PGC-1alpha, a critical determinant of mitochondrial biogenesis. These results suggest that activation of mTORC1 might be beneficial to skeletal muscle by providing resistance to muscle atrophy and increasing oxidative function. Here, we tested this hypothesis by deletion of the mTORC1 inhibitor tuberous sclerosis complex (TSC) in muscle fibers. METHOD: Skeletal muscles of mice with an acute or a permanent deletion of raptor or TSC1 were examined using histological, biochemical and molecular biological methods. Response of the muscles to changes in mechanical load and nerve input was investigated by challenging the mice by denervation or ablation of synergistic muscles. RESULTS: Genetic deletion or knockdown of raptor, causing inactivation of mTORC1, was sufficient to prevent muscle growth and enhance muscle atrophy. Conversely, short-term activation of mTORC1 by knockdown of TSC induced muscle fiber hypertrophy and atrophy-resistance upon denervation, in both fast tibialis anterior (TA) and slow soleus muscles. Surprisingly, however, sustained activation of mTORC1 by genetic deletion of Tsc1 caused muscle atrophy in all but soleus muscles. In contrast, oxidative capacity was increased in all muscles examined. Consistently, TSC1-deficient soleus muscle was atrophy-resistant whereas TA underwent normal atrophy upon denervation. Moreover, upon overloading, plantaris muscle did not display enhanced hypertrophy compared to controls. Biochemical analysis indicated that the atrophy respo of muscles was based on the suppressed phosphorylation of PKB/Akt via feedback inhibition by mTORC1 and subsequent increased expression of the E3 ubiquitin ligases MuRF1 and atrogin-1/MAFbx. In contrast, expression of both E3 ligases was not increased in soleus muscle suggesting the presence of compensatory mechanisms in this muscle. CONCLUSIONS: Our study shows that the mTORC1- and the PKB/Akt-FoxO pathways are tightly interconnected and differentially regulated depending on the muscle type. These results indicate that long-term activation of the mTORC1 signaling axis is not a therapeutic option to promote muscle growth because of its strong feedback induction of the E3 ubiquitin ligases involved in protein degradation
Current directions in videoconferencing tele-mental health research
No full textThe provision of mental health services via videoconferencing tele-mental health has become an increasingly routine component of mental health service delivery throughout the world. Emphasizing the research literature since 2003, we examine (a) the extent to which the field of tele-mental health has advanced the research agenda previously suggested and (b) implications for tele-mental healthcare delivery for special clinical populations. Previous findings have demonstrated that tele-mental health services are satisfactory to patients, improve outcomes, and are probably cost effective. In the very small number of randomized controlled studies that have been conducted to date, tele-mental health has demonstrated equivalent efficacy compared to face-to-face care in a variety of clinical settings and with specific patient populations. However, methodologically flawed or limited research studies are the norm, and thus the research agenda for tele-mental health has not been fully maximized. Implications for future research and practice are discussed
A framework for artificial intelligence in cancer research and precision oncology
No full textArtificial intelligence; Precision oncologyIntel·ligència artificial; Oncologia de precisióInteligencia artificial; Oncología de precisiónR.P.L. is supported by LaCaixa Foundation, a CRIS Foundation Talent Award (TALENT19-05), the FERO Foundation, the Instituto de Salud Carlos III-Investigacion en Salud (PI18/01395 and PI21/01019), the Prostate Cancer Foundation (18YOUN19) and the Asociación Española Contra el Cancer (AECC) (PRYCO211023SERR, funding C.M.). J.N.K. is supported by the German Federal Ministry of Health (DEEP LIVER, ZMVI1-2520DAT111) and the Max-Eder-Program of the German Cancer Aid (grant #70113864), the German Federal Ministry of Education and Research (PEARL, 01KD2104C; CAMINO, 01EO2101; SWAG, 01KD2215A; TRANSFORM LIVER, 031L0312A; TANGERINE, 01KT2302 through ERA-NET Transcan), the German Academic Exchange Service (SECAI, 57616814), the German Federal Joint Committee (Transplant.KI, 01VSF21048) the European Union’s Horizon Europe and innovation program (ODELIA, 101057091; GENIAL, 101096312) and the National Institute for Health and Care Research (NIHR, NIHR213331) Leeds Biomedical Research Centre. JSR-F is funded in part by the Breast Cancer Research Foundation, a Susan G Komen Leadership grant, an NIH/NCI P50 CA247749 01 grant, and an NIH/NCI grant No. P30CA008748. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care
Bench-to-bedside review: Erythropoietin and its derivatives as therapies in critical care
No full textAuthor can archive publisher's pdf. Free via Creative Commons: CC-BENCHTOBEDSIDE-2.0. © 2012 BioMed Central Ltd
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