Triple-negative breast cancer (TNBC) lacks prognostic and predictive markers. Here, we use high-throughput phosphoproteomics to build a functional TNBC taxonomy. A cluster of 159 phosphosites is ...upregulated in relapsed cases of a training set (n = 34 patients), with 11 hyperactive kinases accounting for this phosphoprofile. A mass-spectrometry-to-immunohistochemistry translation step, assessing 2 independent validation sets, reveals 6 kinases with preserved independent prognostic value. The kinases split the validation set into two patterns: one without hyperactive kinases being associated with a >90% relapse-free rate, and the other one showing ≥1 hyperactive kinase and being associated with an up to 9.5-fold higher relapse risk. Each kinase pattern encompasses different mutational patterns, simplifying mutation-based taxonomy. Drug regimens designed based on these 6 kinases show promising antitumour activity in TNBC cell lines and patient-derived xenografts. In summary, the present study elucidates phosphosites and kinases implicated in TNBC and suggests a target-based clinical classification system for TNBC.
Introduction
Ageing leads to physiological cognitive decline that it is worsened in people with neurodegenerative diseases such as Alzheimer's disease. Despite the ongoing search for a solution to ...this cognitive decline, no effective remedies have been established. It has been determined that modifiable external factors, such as oral health and occlusal function, prevent cognitive decline.
Objective
To analyse the primary interactions between occlusal function and cognitive functions.
Main findings
Masticatory function is related to cognitive functions. In particular, current evidence, from both animal and human studies, suggests that the activation of masticatory muscles and proper mastication, with natural teeth or dental prosthesis, induces the release of several mediators and the activation of specific brain areas. Together, they result in higher neuronal activity, neurotrophic support, blood flow and the prevention of amyloid‐beta plaque formation. Thus, all the components of the masticatory system must work together in order to preserve cognitive function.
Conclusions
Available evidence suggests that oral and cognitive health are more interconnected than previously thought. Therefore, maintenance and adequate restoration of the whole masticatory system are important for the prevention of cognitive decline. In summary, oral and chewing health lead to healthy cognitive ageing.
Bioactive supplements display relevant therapeutic properties when properly applied according to validated molecular effects. Our previous research efforts established the basis to develop a dietary ...supplement based on a
supercritical extract. This was enriched in phenolic diterpenes (RE) with proven properties against signaling pathways involved in colon tumorigenesis, and shark liver oil rich in alkylglycerols (AKG) as a bioactive lipid vehicle to improve RE bioavailability and synergize with the potential therapeutic action of the extract. Herein, we have investigated the tolerability and safety of the supplement and the biological and molecular effects from an immuno-nutritional perspective. Sixty healthy volunteers participated in a six week, double-blind, randomized parallel pilot study with two study arms: RE-AKG capsules (CR) and control capsules (CC). Mean age (±SD) of volunteers was 28.32 (±11.39) and 27.5 (±9.04) for the control and the study groups, respectively. Safety of the CR product consumption was confirmed by analyzing liver profile, vital constants, and oxidation markers (LDLox in blood and isoprostanes and thromboxanes in urine). The following were monitored: (1) the phenotyping of plasmatic leukocytes and the ex vivo response of lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs); (2) expression of genes associated with immune-modulation, inflammation, oxidative stress, lipid metabolism, and tumorigenesis; and (3) the correlation of selected genetic variants (SNPs) with the differential responses among individuals. The lack of adverse effects on liver profile and oxidation markers, together with adequate tolerability and safe immunological adaptations, provide high-quality information for the potential use of CR as co-adjuvant of therapeutic strategies against colorectal cancer.
The landscape of academic publishing is marked by a diverse array of journals, each with its distinct scope, focus, reach and impact. In the pursuit of disseminating research findings, contributing ...to the collective body of knowledge and gain recognition, researchers are confronted with the pivotal decision of where to publish their work. While international journals attract attention for their global reach, legibility and impact factor, the significance of prioritizing publication in local journals need not be underestimated. This document aims to underscore the importance of embracing local journals as a priority in the realm of scholarly dissemination, emphasizing their unique contributions to scientific advancement, community engagement, and the holistic progression of research endeavors.
Amid the global pandemic crisis, international concern has centered on the control and prevention measures aimed at reducing the speed of the virus transmission while a more radical sanitary measure, ...such as vaccines, is achieved. Governmental and social efforts have had great impact on various sectors of society and their consequences have exceeded the sphere of health.
This essay discusses the scope of specific measures in the sense of the appropriation of risk control measures and proposes the epidemiological method as an alternative that goes beyond the quantification of risks and the attribution of responsibilities. To conclude, the emphasis is placed on the need to promote information about socialization processes to better understand the consequences of individual acts favoring alternatives other than pandemic control based on the use of coercive measures.
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐Cov‐2) has led to the elaboration of multiple studies to increase knowledge and understanding, hence, having the ability ...to accomplish an adequate and timely diagnosis and give an optimal treatment according to the patient's condition. The clinical manifestations of COVID‐19 pose a series of challenges both in understanding and delimiting the disease secondary to the SARS‐CoV‐2 infection. This is due to the fact that the main axis of this disease is the endothelial compromise and the production of a “cytokine storm,” triggering multiple organ failure and death. Given that a complete understanding of its pathophysiology and clinical behavior has not yet been achieved, we wondered if coinfection with other respiratory viruses modifies its performance and outcomes described so far. A literature search was performed, obtaining 68 articles, of which 25 were analyzed. The analysis showed us that there is a high variety both in the types of associated infections and in the clinical behavior of patients and their outcomes. Therefore, we consider that the search for other infections should be performed exhaustively, especially in those cases that may be susceptible to treatment such as Influenza A, human immunodeficiency virus, or bacterial infections. As well as optimize the analysis of these cases and establish if there are characteristics that allow establishing the possibility of carrying an additional infection to that of SARS‐CoV‐2 and the implications for the management and prognosis of the patient.
Multimorbidity (MM) prevalence among older adults is increasing worldwide. Variations regarding the socioeconomic characteristics of the individuals and their context have been described, mostly in ...high-income settings. However, further research is needed to understand the effect of the coexistence of infectious diseases along with socioeconomic factors regarding MM. This study aims to examine the variation of MM regarding infectious diseases mortality after adjusting for socioeconomic factors. A cross-sectional multilevel study with a nationally representative sample of 17,571 Colombian adults of 60 years of age or older was conducted. Individual socioeconomic, demographic, childhood and health related characteristics, as well as group level variables (multidimensional poverty index and infectious diseases mortality rate) were analyzed. A two-level stepwise structural equation model was used to simultaneously adjust for the individual and contextual effects. Multimorbidity prevalence was 62.3% (95% CI 61.7-62.9). In the multilevel adjusted models, age, female sex, having functional limitations, non-white ethnicity, high body mass index, higher income, physical inactivity and living in urban areas were associated with multimorbidity among the sample for this study. The median odds ratio for multidimensional poverty was 1.18 (1.16-1.19; p = 0.008) and for infectious diseases was 1.25 (1.22-1.28; p = 0.014). This paper demonstrates that MM varies regarding the mortality of infectious diseases and shows a strong association between MM and poverty in a low-middle income country. Differences in the factors involved in the etiology of multimorbidity are expected among wealthy and poor countries regarding availability and prioritization of health services.
To analyze the behavior temporal of road-traffic injuries (RTI) in Valledupar, Colombia from January 2008 to December 2012.
An observational study was conducted based on records from the Colombian ...National Legal Medicine and Forensic Sciences Institute regional office in Valledupar. Different variables were analyzed, such as the injured person's sex, age, education level, and type of road user; the timeframe, place and circumstances of crashes and the vehicles associated with the occurrence. Furthermore, a time series analysis was conducted using an auto-regressive integrated moving average.
There were 105 events per month on an average, 64.9% of RTI involved men; 82.3% of the persons injured were from 18 to 59 years of age; the average age was 35.4 years of age; the road users most involved in RTI were motorcyclists (69%), followed by pedestrians (12%). 70% had up to upper-secondary education. Sunday was the day with the most RTI occurrences; 93% of the RTI occurred in the urban area. The time series showed a seasonal pattern and a significant trend effect. The modeling process verified the existence of both memory and extrinsic variables related.
An RTI occurrence pattern was identified, which showed an upward trend during the period analyzed. Motorcyclists were the main road users involved in RTI, which suggests the need to design and implement specific measures for that type of road user, from regulations for graduated licensing for young drivers to monitoring road user behavior for the promotion of road safety.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To estimate the prevalence of musculoskeletal (MSK) disorders and to describe predicting variables associated with rheumatic diseases in 5 regions of México.
This was a cross-sectional, ...community-based study performed in 5 regions in México. The methodology followed the guidelines proposed by the Community Oriented Program for the Control of the Rheumatic Diseases (COPCORD). A standardized methodology was used at all sites, with trained personnel following a common protocol of interviewing adult subjects in their household. A "positive case" was defined as an individual with nontraumatic MSK pain of > 1 on a visual analog pain scale (0 to 10) during the last 7 days. All positive cases were referred to internists or rheumatologists for further clinical evaluation, diagnosis, and proper treatment.
The study included 19,213 individuals; 11,602 (68.8%) were female, and their mean age was 42.8 (SD 17.9) years. The prevalence of MSK pain was 25.5%, but significant variations (7.1% to 43.5%) across geographical regions occurred. The prevalence of osteoarthritis was 10.5%, back pain 5.8%, rheumatic regional pain syndromes 3.8%, rheumatoid arthritis 1.6%, fibromyalgia 0.7%, and gout 0.3%. The prevalence of MSK manifestations was associated with older age and female gender.
The prevalence of MSK pain in our study was 25.5%. Geographic variations in the prevalence of MSK pain and specific diagnoses suggested a role for geographic factors in the prevalence of rheumatic diseases.
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