1,290 research outputs found
Chemoprevention agents to reduce mammographic breast density in premenopausal women: A systematic review of clinical trials
Background: Higher mammographic breast density (MBD) is associated with an increased risk of breast cancer when compared with lower MBD, especially in premenopausal women. However, little is known about the effectiveness of chemoprevention agents in reducing MBD in premenopausal women without a history of breast cancer. Findings from this review should provide insight on how to target MBD in breast cancer prevention in premenopausal women with dense breasts.
Methods: We searched 9 electronic databases for clinical trials in English, Spanish, French, or German published until January 2020. Articles evaluating the association of pharmacological agents and MBD were included. Data were extracted on methods, type and dose of intervention, outcomes, side effects, and follow up. Quality of the studies was assessed using the US Preventive Services Task Force criteria.
Results: We identified 7 clinical trials evaluating the associations of 6 chemoprevention agents with changes in MBD in premenopausal women without history of breast cancer. The studies evaluated selective estrogen-receptor modulators (n = 1); gonadotropin-releasing hormone agonists (n = 2); isoflavones (n = 1); vitamin D (n = 1); and Boswellia, betaine, and mayo-inositol compound (n = 1). Hormonal interventions were associated with net reductions in percent density (tamoxifen [13.4%], leuprolide acetate [8.9%], and goserelin [2.7%]), whereas nonhormonal (vitamin D and isoflavone) interventions were not. However, MBD returned to preintervention baseline levels after cessation of gonadotropin-releasing hormone agonists.
Conclusions: A limited number of chemoprevention agents have been shown to reduce MBD in premenopausal women. Identification of new and well-tolerated chemoprevention agents targeting MBD and larger studies to confirm agents that have been studied in small trials are urgent priorities for primary breast cancer prevention in premenopausal women with dense breasts
Post-stroke patients functional task characterization through accelerometry data for rehabilitation intervention and monitoring
An increasing ageing society and consequently rising number ofpost-stroke related neurological dysfunction patients are forcing therehabilitation field to adapt to ever-growing demands. Compensatorymovements related to available motor strategies, can be observed inpost-stroke patients when performing functional tasks due to apathological synergy as in reaching for an object. Studies of post-strokemotor recovery suggest that such maladaptive strategies may limit theplasticity of the nervous system to enhance neuromotor recovery.Strategies for rehabilitation protocols monitoring and validation arepresently a necessity, moreover considering data recording is oftenabsent of the rehabilitation process or subjective in nature.Characterization strategies of patient performance during functional taskare key aspects for clinical protocols validation, progress monitoring andmethodologies comparison. This project seeks to characterize patientsupper limb performance through accelerometry, gathered with a lowcostwearable system, for compensatory movement avoidance throughfeedback response
Developments and opportunities in fungal strain engineering for the production of novel enzymes and enzyme cocktails for plant biomass degradation
Fungal strain engineering is commonly used in many areas of biotechnology, including the production of plant biomass degrading enzymes. Its aim varies from the production of specific enzymes to overall increased enzyme production levels and modification of the composition of the enzyme set that is produced by the fungus. Strain engineering involves a diverse range of methodologies, including classical mutagenesis, genetic engineering and genome editing. In this review, the main approaches for strain engineering of filamentous fungi in the field of plant biomass degradation will be discussed, including recent and not yet implemented methods, such as CRISPR/Cas9 genome editing and adaptive evolution.Peer reviewe
Non-viral Gene Delivery Methods for Bone and Joints.
Viral carrier transport efficiency of gene delivery is high, depending on the type of vector. However, viral delivery poses significant safety concerns such as inefficient/unpredictable reprogramming outcomes, genomic integration, as well as unwarranted immune responses and toxicity. Thus, non-viral gene delivery methods are more feasible for translation as these allow safer delivery of genes and can modulate gene expression transiently both in vivo, ex vivo, and in vitro. Based on current studies, the efficiency of these technologies appears to be more limited, but they are appealing for clinical translation. This review presents a summary of recent advancements in orthopedics, where primarily bone and joints from the musculoskeletal apparatus were targeted. In connective tissues, which are known to have a poor healing capacity, and have a relatively low cell-density, i.e., articular cartilage, bone, and the intervertebral disk (IVD) several approaches have recently been undertaken. We provide a brief overview of the existing technologies, using nano-spheres/engineered vesicles, lipofection, and in vivo electroporation. Here, delivery for microRNA (miRNA), and silencing RNA (siRNA) and DNA plasmids will be discussed. Recent studies will be summarized that aimed to improve regeneration of these tissues, involving the delivery of bone morphogenic proteins (BMPs), such as BMP2 for improvement of bone healing. For articular cartilage/osteochondral junction, non-viral methods concentrate on targeted delivery to chondrocytes or MSCs for tissue engineering-based approaches. For the IVD, growth factors such as GDF5 or GDF6 or developmental transcription factors such as Brachyury or FOXF1 seem to be of high clinical interest. However, the most efficient method of gene transfer is still elusive, as several preclinical studies have reported many different non-viral methods and clinical translation of these techniques still needs to be validated. Here we discuss the non-viral methods applied for bone and joint and propose methods that can be promising in clinical use
Low-Cost Wearable Data Acquisition for Stroke Rehabilitation: A Proof-of-Concept Study on Accelerometry for Functional Task Assessment
Background: An increasingly aging society and consequently rising number of patients with poststroke-related neurological dysfunctions are forcing the rehabilitation field to adapt to ever-growing demands. Although clinical reasoning within rehabilitation is dependent on patient movement performance analysis, current strategies for monitoring rehabilitation progress are based on subjective time-consuming assessment scales, not often applied. Therefore, a need exists for efficient nonsubjective monitoring methods. Wearable monitoring devices are rapidly becoming a recognized option in rehabilitation for quantitative measures. Developments in sensors, embedded technology, and smart textile are driving rehabilitation to adopt an objective, seamless, efficient, and cost-effective delivery system. This study aims to assist physiotherapists’ clinical reasoning process through the incorporation of accelerometers as part of an electronic data acquisition system. Methods: A simple, low-cost, wearable device for poststroke rehabilitation progress monitoring was developed based on commercially available inertial sensors. Accelerometry data acquisition was performed for 4 first-time poststroke patients during a reach-press-return task. Results: Preliminary studies revealed acceleration profiles of stroke patients through which it is possible to quantitatively assess the functional movement, identify compensatory strategies, and help define proper movement. Conclusion: An inertial data acquisition system was designed and developed as a low-cost option for monitoring rehabilitation. The device seeks to ease the data-gathering process by physiotherapists to complement current practices with accelerometry profiles and aid the development of quantifiable methodologies and protocols.info:eu-repo/semantics/publishedVersio
Potential missed opportunities for diagnosis of cryptococcosis and the association with mortality: A cohort study
BACKGROUND: Cryptococcosis is one of the most common life-threatening opportunistic mycoses worldwide. Insidious presentation and slow onset of symptoms make it difficult to recognize, complicating the diagnostic process. Delays in diagnosis may lead to increased mortality. We aim to determine the frequency of missed opportunities for diagnosis of cryptococcosis and its effects on mortality.
METHODS: To estimate the proportion of individuals with a potentially missed diagnosis for cryptococcosis in hospitalized patients, we conducted a retrospective cohort study using the Healthcare Cost and Utilization Project State Inpatient Databases from 2005 to 2015 from eight states. All hospitalized adult patients diagnosed with cryptococcal infection or cryptococcal meningitis were included. Potentially missed diagnoses were defined as admissions coded for a procedure or diagnosis suggestive of cryptococcosis in the 90-days prior to the initial cryptococcosis admission. Generalized estimating equations models were used to evaluate the association between underlying comorbidities and potential missed diagnosis of cryptococcosis and 90-day all-cause in-hospital mortality.
FINDINGS: Of 5,354 patients with cryptococcosis, 2,445 (45·7%) were people living with HIV (PLWH). Among PLWH, 493/2,445 (20·2%) had a potentially missed diagnosis, of which 83/493 (16·8%) died while hospitalized compared with 265/1,952 (13·6%) of those without a potentially missed diagnosis (relative risk [RR] 1·04, 95% CI 0·99-1·09). Among HIV-negative patients, 977/2,909 (33·6%) had a potentially missed diagnosis, of which 236/977 (24·2%) died while hospitalized compared with 298/1,932 (15·4%) of those not missed (RR 1·12, 95% CI 1·07-1·16).
INTERPRETATION: Missed opportunities to diagnose cryptococcosis are common despite highly efficacious diagnostic tests and are associated with increased risk of 90-day mortality in HIV-negative patients. A high index of clinical suspicion is paramount to promptly diagnose, treat, and improve cryptococcosis-related mortality.
FUNDING: National Center for Advancing Translational Sciences, Washington University Institute of Clinical and Translational Sciences, and the Agency for Healthcare Research and Quality
Neurocognitive Functioning in Individuals at Clinical High Risk for Psychosis
IMPORTANCE: Neurocognitive functioning is a potential biomarker to advance detection, prognosis, and preventive care for individuals at clinical high risk for psychosis (CHR-P). The current consistency and magnitude of neurocognitive functioning in individuals at CHR-P are undetermined. OBJECTIVE: To provide an updated synthesis of evidence on the consistency and magnitude of neurocognitive functioning in individuals at CHR-P. DATA SOURCES: Web of Science database, Cochrane Central Register of Reviews, and Ovid/PsycINFO and trial registries up to July 1, 2020. STUDY SELECTION: Multistep literature search compliant with Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology performed by independent researchers to identify original studies reporting on neurocognitive functioning in individuals at CHR-P. DATA EXTRACTION AND SYNTHESIS: Independent researchers extracted the data, clustering the neurocognitive tasks according to 7 Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) domains and 8 CHR-P domains. Random-effect model meta-analyses, assessment of publication biases and study quality, and meta-regressions were conducted. MAIN OUTCOMES AND MEASURES: The primary effect size measure was Hedges g of neurocognitive functioning in individuals at CHR-P (1) compared with healthy control (HC) individuals or (2) compared with individuals with first-episode psychosis (FEP) or (3) stratified for the longitudinal transition to psychosis. RESULTS: A total of 78 independent studies were included, consisting of 5162 individuals at CHR-P (mean [SD; range] age, 20.2 [3.3; 12.0-29.0] years; 2529 [49.0%] were female), 2865 HC individuals (mean [SD; range] age, 21.1 [3.6; 12.6-29.2] years; 1490 [52.0%] were female), and 486 individuals with FEP (mean [SD; range] age, 23.0 [2.0; 19.1-26.4] years; 267 [55.9%] were female). Compared with HC individuals, individuals at CHR-P showed medium to large deficits on the Stroop color word reading task (g = −1.17; 95% CI, −1.86 to −0.48), Hopkins Verbal Learning Test–Revised (g = −0.86; 95% CI, −1.43 to −0.28), digit symbol coding test (g = −0.74; 95% CI, −1.19 to −0.29), Brief Assessment of Cognition Scale Symbol Coding (g = −0.67; 95% CI, −0.95 to −0.39), University of Pennsylvania Smell Identification Test (g = −0.55; 95% CI, −0.97 to −0.12), Hinting Task (g = −0.53; 95% CI, −0.77 to −0.28), Rey Auditory Verbal Learning Test (g = −0.50; 95% CI, −0.78 to −0.21), California Verbal Learning Test (CVLT) (g = −0.50; 95% CI, −0.64 to −0.36), and National Adult Reading Test (g = −0.52; 95% CI, −1.01 to −0.03). Individuals at CHR-P were less impaired than individuals with FEP. Longitudinal transition to psychosis from a CHR-P state was associated with medium to large deficits in the CVLT task (g = −0.58; 95% CI, −1.12 to −0.05). Meta-regressions found significant effects for age and education on processing speed. CONCLUSIONS AND RELEVANCE: Findings from this meta-analysis support neurocognitive dysfunction as a potential detection and prognostic biomarker in individuals at CHR-P. These findings may advance clinical research and inform preventive approaches
TecnologÃa apropiada para la generación de sistemas constructivos
Este trabajo realizado durante el PAP de TecnologÃa apropiada para la generación de sistemas constructivos presenta los resultados de las pruebas realizadas a los distintos sistemas constructivos a base de tierra que fueron utilizados durante este periodo de otoño, probando suelos de Chiquilistlán, Sierra de Quila y Palo Alto. Además, se analiza su uso en las distintas comunidades según los recursos que se encuentren a la mano dependiendo de la región para poder ayudar en su desarrollo urbano y promover que los habitantes utilicen diferentes métodos de construcción a los que se usan convencionalmente y de igual forma se expresa en este documento ciertas problemáticas que existen actualmente en la localidad de Palo Alto y Sierra de Quila, asà como las posibles soluciones que se les están presentando. Aunado a esto, se presentan. De igual forma, este documento presenta una revisión de daños estructurales en cuatro mercados diferentes de la Zona Metropolitana de Guadalajara, Jalisco que se realizó con ayuda del IMEPLAN.ITESO, A.C
Fucoidan from Fucus vesiculosus inhibits inflammatory response, both in vitro and in vivo
Fucoidan has been reported to present diverse bioactivities, but each extract has specific
features from which a particular biological activity, such as immunomodulation, must be confirmed.
In this study a commercially available pharmaceutical-grade fucoidan extracted from Fucus vesiculosus,
FE, was characterized and its anti-inflammatory potential was investigated. Fucose was the main
monosaccharide (90 mol%) present in the studied FE, followed by uronic acids, galactose, and
xylose that were present at similar values (3.8–2.4 mol%). FE showed a molecular weight of 70 kDa
and a sulfate content of around 10%. The expression of cytokines by mouse bone-marrow-derived
macrophages (BMDMs) revealed that the addition of FE upregulated the expression of CD206 and
IL-10 by about 28 and 22 fold, respectively, in respect to control. This was corroborated in a stimulated
pro-inflammatory situation, with the higher expression (60 fold) of iNOS being almost completely
reversed by the addition of FE. FE was also capable of reverse LPS-caused inflammation in an in vivo
mouse model, including by reducing macrophage activation by LPS from 41% of positive CD11C to
9% upon fucoidan injection. Taken together, the potential of FE as an anti-inflammatory agent was
validated, both in vitro and in vivo.This research received funding from project 0474_BLUEBIOLAB_1_E, financed by the European Regional Development Fund through INTERREG España-Portugal 2014–2020, and project ATLANTIDA (ref. NORTE-01-0145-FEDER-000040) supported by the Northern Portugal Regional Programme Norte 2020, under the Portugal 2020 Partnership Agreement. This work was also developed within the scope of the project CICECO-Aveiro Institute of Materials (UIDB/50011/2020, UIDP/50011/2020 and LA/P/0006/2020) and LAQV-REQUIMTE (UIDB/50006/2020), financed by national funds of the Portuguese Foundation for Science and Technology (FCT)/MCTES. A. S. F. thanks FCT for the individual grant (SFRH/BD/102471/2014). This work was also funded by national funds (OE), through FCT, I.P., within the scope of the framework contract seen in numbers 4, 5 and 6 of article 23 of the Decree Law 57/2016, August 29, changed by Law 57/2017, July 19. The authors are also thankful to the financial support from the Natural Science Foundation of China (grant No. 32000936)
Neural Working Memory Changes During a Spaceflight Analog With Elevated Carbon Dioxide: A Pilot Study
Spaceflight missions to the International Space Station (ISS) expose astronauts to
microgravity, radiation, isolation, and elevated carbon dioxide (COâ‚‚), among other
factors. Head down tilt bed rest (HDBR) is an Earth-based analog for spaceflight used to
study body unloading, fluid shifts, and other factors unrelated to gravitational changes.
While in space, astronauts need to use mental rotation strategies to facilitate their
adaptation to the ISS environment. Therefore, spatial working memory is essential for
crewmember performance. Although the effects of HDBR on spatial working memory
have recently been studied, the results are still inconclusive. Here, we expand upon
past work and examine the effects of HDBR with elevated COâ‚‚ (HDBR + COâ‚‚) on
brain activation patterns during spatial working memory performance. In addition,
we compare brain activation between 30 days of HDBR + COâ‚‚ and 70 days of
HDBR to test the isolated effect of COâ‚‚. Eleven subjects (6 males, 5 females; mean
age = 34 ± 8 years) underwent six functional magnetic resonance imaging (fMRI)
sessions pre-, during, and post-HDBR + COâ‚‚. During the HDBR + COâ‚‚ intervention,
we observed decreasing activation in the right middle frontal gyrus and left regions of
the cerebellum, followed by post-intervention recovery. We detected several correlations
between brain and behavioral slopes of change with the HDBR + COâ‚‚ intervention.
For example, greater increases in activation in frontal, temporal and parietal regions
were associated with larger spatial working memory improvements. Comparing the
HDBR + COâ‚‚ group to data from our previous 70-day HDBR study, we found greater
decreases in activation in the right hippocampus and left inferior temporal gyrus for
the HDBR + COâ‚‚ group over the course of the intervention. Together, these findings
increase our understanding of the neural mechanisms of HDBR, elevated levels of COâ‚‚
and spaceflight-related changes in spatial working memory performance
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