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1.
Cell ; 176(3): 610-624.e18, 2019 01 24.
Article in English | MEDLINE | ID: mdl-30612739

ABSTRACT

Plasma cells (PC) are found in the CNS of multiple sclerosis (MS) patients, yet their source and role in MS remains unclear. We find that some PC in the CNS of mice with experimental autoimmune encephalomyelitis (EAE) originate in the gut and produce immunoglobulin A (IgA). Moreover, we show that IgA+ PC are dramatically reduced in the gut during EAE, and likewise, a reduction in IgA-bound fecal bacteria is seen in MS patients during disease relapse. Removal of plasmablast (PB) plus PC resulted in exacerbated EAE that was normalized by the introduction of gut-derived IgA+ PC. Furthermore, mice with an over-abundance of IgA+ PB and/or PC were specifically resistant to the effector stage of EAE, and expression of interleukin (IL)-10 by PB plus PC was necessary and sufficient to confer resistance. Our data show that IgA+ PB and/or PC mobilized from the gut play an unexpected role in suppressing neuroinflammation.


Subject(s)
Immunoglobulin A/metabolism , Interleukin-10/metabolism , Intestines/immunology , Animals , Encephalomyelitis, Autoimmune, Experimental/immunology , Humans , Immunoglobulin A/immunology , Intestinal Mucosa/metabolism , Mice , Mice, Inbred C57BL , Multiple Sclerosis/immunology , Neuroimmunomodulation/immunology , Plasma Cells/metabolism
3.
J Immunol ; 212(6): 1022-1028, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38294253

ABSTRACT

Plasma cells secrete an abundance of Abs and are a crucial component of our immune system. The intestinal lamina propria harbors the largest population of plasma cells, most of which produce IgA. These Abs can bind to beneficial gut bacteria to reinforce intestinal homeostasis and provide protection against enteric pathogens. Plasma cells downregulate many cell-surface proteins commonly used to identify B cells. In mice, expression of the surface marker CD138 has been widely used to identify plasma cells in lymph nodes, bone marrow, and spleen. Intestinal plasma cells require liberation via extensive tissue processing involving treatment with collagenase. We report that detection of CD138 surface expression is reduced following collagenase treatment. Using a mouse in which yellow fluorescent protein expression is controlled by the plasma cell requisite transcription factor Blimp-1, we show that surface detection of transmembrane activator and CAML interactor captures a significant proportion of Ab-secreting plasma cells in the intestinal lamina propria and gut-draining mesenteric lymph nodes. Additionally, we describe a flow cytometry panel based on the detection of surface markers to identify murine B cell subsets in the intestinal lamina propria and, as a proof of concept, combine it with a cutting-edge fate-tracking system to characterize the fate of germinal center B cells activated in early life. By identifying plasma cells and other key intestinal B subsets in a manner compatible with several downstream applications, including sorting and culturing and in vitro manipulations, this efficient and powerful approach can enhance studies of mucosal immunity.


Subject(s)
Immunoglobulin A , Plasma Cells , Animals , Mice , B-Lymphocytes , Collagenases/metabolism , Mucous Membrane , Intestinal Mucosa
4.
Curr Opin Rheumatol ; 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39264338

ABSTRACT

PURPOSE OF REVIEW: Systemic vasculitides are characterized by inflammation of blood vessels. Their classification is based on the size of the blood vessels involved - large, medium, or small. Vasculitis early diagnosis and reliable monitoring are crucial to establish a treatment plan and prevent serious complications. Based on these considerations and depending on the location of the affected vessels, the importance of imaging modalities including ultrasonography (US), magnetic resonance Imaging (MRI), magnetic resonance angiography (MRA), computed tomography (CT), computed tomography angiography (CTA), and [18F]-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) has progressively increased. In addition to physical exam and laboratory data, these imaging tools offer complementary information about vascular changes occurring in vasculitis.This review summarizes the different imaging modalities being utilized to diagnose and monitor vasculitis. RECENT FINDINGS: The most recent update for the use of imaging in vasculitis is referenced in the 2023 European Alliance of Associations for Rheumatology (EULAR) recommendations and the American College of Rheumatology (ACR) guidelines in 2021. Recent advances in PET imaging in large vessel vasculitis include improved technological imaging acquisition and the use of novel radiotracers for cellular and immune targets. FDG-PET has now been demonstrated to have high sensitivity and specificity to detect temporal arteritis. SUMMARY: Imaging plays a significant role in the evaluation of vasculitis and continues to gain importance in the diagnosis and monitoring of disease activity. Differences exist between the ACR guidelines, which advocates for temporal artery biopsy, and the EULAR guidelines, which favors imaging modalities for the initial evaluation and diagnosis of large vessel vasculitis (LVV). Prerequisites for appropriate clinical management utilizing imaging in patients with vasculitis are the availability and access to skilled clinicians to interpret the images and the cost of these techniques not being prohibitive.

5.
Bioinformatics ; 39(11)2023 11 01.
Article in English | MEDLINE | ID: mdl-37935419

ABSTRACT

MOTIVATION: Accurate prediction of change in protein stability due to point mutations is an attractive goal that remains unachieved. Despite the high interest in this area, little consideration has been given to the transformer architecture, which is dominant in many fields of machine learning. RESULTS: In this work, we introduce PROSTATA, a predictive model built in a knowledge-transfer fashion on a new curated dataset. PROSTATA demonstrates advantage over existing solutions based on neural networks. We show that the large improvement margin is due to both the architecture of the model and the quality of the new training dataset. This work opens up opportunities to develop new lightweight and accurate models for protein stability assessment. AVAILABILITY AND IMPLEMENTATION: PROSTATA is available at https://github.com/AIRI-Institute/PROSTATA and https://prostata.airi.net.


Subject(s)
Machine Learning , Neural Networks, Computer , Point Mutation , Protein Stability
6.
Anesthesiology ; 140(1): 8-24, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37713506

ABSTRACT

BACKGROUND: In previous analyses, myocardial injury after noncardiac surgery, major bleeding, and sepsis were independently associated with most deaths in the 30 days after noncardiac surgery, but most of these deaths occurred during the index hospitalization for surgery. The authors set out to describe outcomes after discharge from hospital up to 1 yr after inpatient noncardiac surgery and associations between predischarge complications and postdischarge death up to 1 yr after surgery. METHODS: This study was an analysis of patients discharged after inpatient noncardiac surgery in a large international prospective cohort study across 28 centers from 2007 to 2013 of patients aged 45 yr or older followed to 1 yr after surgery. The study estimated (1) the cumulative postdischarge incidence of death and other outcomes up to a year after surgery and (2) the adjusted time-varying associations between postdischarge death and predischarge complications including myocardial injury after noncardiac surgery, major bleeding, sepsis, infection without sepsis, stroke, congestive heart failure, clinically important atrial fibrillation or flutter, amputation, venous thromboembolism, and acute kidney injury managed with dialysis. RESULTS: Among 38,898 patients discharged after surgery, the cumulative 1-yr incidence was 5.8% (95% CI, 5.5 to 6.0%) for all-cause death and 24.7% (95% CI, 24.2 to 25.1%) for all-cause hospital readmission. Predischarge complications were associated with 33.7% (95% CI, 27.2 to 40.2%) of deaths up to 30 days after discharge and 15.0% (95% CI, 12.0 to 17.9%) up to 1 yr. Most of the association with death was due to myocardial injury after noncardiac surgery (15.6% [95% CI, 9.3 to 21.9%] of deaths within 30 days, 6.4% [95% CI, 4.1 to 8.7%] within 1 yr), major bleeding (15.0% [95% CI, 8.3 to 21.7%] within 30 days, 4.7% [95% CI, 2.2 to 7.2%] within 1 yr), and sepsis (5.4% [95% CI, 2.2 to 8.6%] within 30 days, 2.1% [95% CI, 1.0 to 3.1%] within 1 yr). CONCLUSIONS: One in 18 patients 45 yr old or older discharged after inpatient noncardiac surgery died within 1 yr, and one quarter were readmitted to the hospital. The risk of death associated with predischarge perioperative complications persists for weeks to months after discharge.


Subject(s)
Patient Discharge , Sepsis , Humans , Prospective Studies , Aftercare , Hemorrhage , Postoperative Complications/epidemiology , Risk Factors
7.
Nephrol Dial Transplant ; 39(4): 648-658, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-37653455

ABSTRACT

BACKGROUND: The aim of this study was to provide an overview of age, sex and primary renal disease (PRD) distribution among first kidney transplant recipients across Europe. METHOD: The European Renal Association (ERA) Registry database was used to obtain data on patients aged 20 years or older receiving their first kidney transplant between 2010 and 2019 from 12 European countries. The numbers and percentages of recipients in each age, sex and PRD group were calculated by country, donor type and year. RESULTS: In total, 99 543 adults received a first kidney transplant. Overall, 23% of the recipients were 65 years or older, 36% were female, and 21% had glomerulonephritis and 15% diabetes mellitus as PRD. Compared with deceased donor kidney transplant recipients, living donor kidney transplant recipients were less often 65 years or older (13% versus 26%), more often had glomerulonephritis (25% versus 20%) and less often diabetes mellitus (8% versus 17%) as PRD. We found large international differences, which were most prominent for age and PRD and less prominent for sex. Over time, the largest change in recipient characteristics was observed for the percentage of recipients aged 65 years or older, increasing from 18% in 2010 to 28% in 2019 for all countries combined with a similar trend in most countries. CONCLUSION: We observed large differences for age and PRD distribution between recipients of living and deceased donor kidneys and between European countries. Over time, the percentage of older first kidney transplant recipients increased.


Subject(s)
Diabetes Mellitus , Glomerulonephritis , Kidney Diseases , Kidney Transplantation , Adult , Humans , Female , Male , Europe , Tissue Donors , Registries , Transplant Recipients , Graft Survival
8.
Article in English | MEDLINE | ID: mdl-38724446

ABSTRACT

BACKGROUND: Preemptive kidney transplantation has better outcomes when compared to transplantation after dialysis. We aimed to examine trends in preemptive kidney transplantation between 2000 and 2019 in Europe and to provide an overview of associated policies, barriers and initiatives. METHODS: Adult patients from 12 European countries who received a preemptive kidney transplant were included. The representatives of the registries providing these data were questioned on the policies, barriers and initiatives around preemptive kidney transplantation. RESULTS: Between 2000 and 2019, 20 251 adults underwent preemptive kidney transplantation (11 169 from living donors, 8937 from deceased donors). The proportion of first kidney transplantations that were preemptive more than doubled from 7% in 2000 to 18% in 2019, reflecting a similar relative increase for living donor kidney recipients (from 21% to 43%) and deceased donor kidney recipients (from 4% to 11%). Large international differences were found. The increase in preemptive kidney transplantation was observed across all age, sex and primary renal disease groups. Countries had similar criteria for preemptive waitlisting. Barriers mentioned included donor shortage, late referral to the transplant center and long donor or recipient work-up. Suggested initiatives included raising awareness on the possibility of preemptive kidney transplantation, earlier start and shorter work-up time for recipient and living donor. CONCLUSIONS: Over the last two decades the proportion of patients receiving a first kidney transplant preemptively has more than doubled, reflecting a similar relative increase for living and deceased donor kidney recipients.

9.
Fish Shellfish Immunol ; 154: 109932, 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39343062

ABSTRACT

There is growing recognition that the hypoxic regions of the ocean are also becoming more acidic due to increasing levels of global carbon dioxide emissions. The impact of water acidification on marine life is largely unknown, as most previous studies have not taken into account the effects of hypoxia, which may affect how organisms respond to low pH levels. In this study, we experimentally examined the consequences of water acidification in combination with normoxic or hypoxic conditions on cellular immune parameters in Mediterranean mussels. We measured total hemocyte counts in hemolymph, the cellular composition of hemolymph, phagocytosis, reactive oxygen species (ROS) production. General response of the organism was evaluated on the basis of the activity of antioxidant enzymes in the hepatopancreas, as well as respiratory rates over an 8-day exposure period. The mussels were exposed to low pH conditions (7.3), either under normoxic conditions (dissolved oxygen concentration of 8 mg/L) or hypoxic conditions (dissolved oxygen concentration of 2 mg/L). The parameters were assessed at days 1, 3, 6, and 8 of the experiment. Experimental acidification under normoxic conditions reduced THC and ROS production by hemocytes during later stages of exposure, but phagocytic activity (PA) only decreased at day 3 and then recovered. Combined acidification and hypoxia suppressed PA in hemocytes at the beginning of exposure, while hemocyte ROS production and THC decreased by the end of the experiment. The hemolymph cellular composition and activity of antioxidant enzymes were unaffected by acidified conditions under different oxygen regimes, but mussel respiratory rate (RR) decreased with a more significant reduction in oxygen consumption under hypoxia. Mussels showed a relatively high tolerance to acidification in combination with various dissolved oxygen levels, although prolonged acidification exposure led to increased detrimental effects on immunity and metabolism.

10.
J Fluoresc ; 34(2): 925-933, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37421567

ABSTRACT

In non-viscous aqueous solutions, the cyanine fluorescent dyes Cy3 and Cy5 have rather low fluorescence efficiency (the fluorescence quantum yields of Cy3 and Cy5 are 0.04 and 0.3, respectively [1, 2]) and short excited state lifetimes due to their structural features. In this work, we investigated the effect of solubility and rotational degrees of freedom on the fluorescence efficiency of Cy3 and Cy5 in several ways. We compared the fluorescence efficiencies of two cyanine dyes sCy3 and sCy5 with the introduction of a sulfonyl substituent in the aromatic ring as well as covalently bound to T10 oligonucleotides. The results show that because of the different lengths of the polymethine chains between the aromatic rings of the dyes, cis-trans-isomerization has a much greater effect on the Cy3 molecule than on the Cy5 molecule, while the effect of aggregation is also significant.

11.
J Urban Health ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38935205

ABSTRACT

In highly urbanized and unequal Latin America, urban health and health equity research are essential to effective policymaking. To ensure the application of relevant and context-specific evidence to efforts to reduce urban health inequities, urban health research in Latin America must incorporate strategic research translation efforts. Beginning in 2017, the Urban Health in Latin America (SALURBAL) project implemented policy-relevant research and engaged policymakers and the public to support the translation of research findings. Over 6 years, more than 200 researchers across eight countries contributed to SALURBAL's interdisciplinary network. This network allowed SALURBAL to adapt research and engagement activities to local contexts and priorities, thereby maximizing the policy relevance of research findings and their application to promote policy action, inform urban interventions, and drive societal change. SALURBAL achieved significant visibility and credibility among academic and nonacademic urban health stakeholders, resulting in the development of evidence and tools to support urban policymakers, planners, and policy development processes across the region. These efforts and their outcomes reveal important lessons regarding maintaining flexibility and accounting for local context in research, ensuring that resources are dedicated to policy engagement and dissemination activities, and recognizing that assessing policy impact requires a nuanced understanding of complex policymaking processes. These reflections are relevant for promoting urban health and health equity research translation across the global south and worldwide. This paper presents SALURBAL's strategy for dissemination and policy translation, highlights innovative initiatives and their outcomes, discusses lessons learned, and shares recommendations for future efforts to promote effective translation of research findings.

12.
J Urban Health ; 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39316308

ABSTRACT

The Care Block of Bogotá, Colombia, is an urban program that offers services for low-income unpaid caregivers. This study aimed to (i) characterize unpaid caregivers' subjective well-being, mental health symptoms, physical activity levels, and use of public spaces linked to the Care Block; (ii) identify caregivers' perceived built and social environment facilitators and barriers to accessing the Care Block facility; and (iii) document the community-led advocacy process to improve the Care Block program. The quantitative component included a subjective well-being and mental health symptoms survey, and the System for Observing Play and Recreation in Communities (SOPARC) instrument. The qualitative component included the Our Voice citizen science method augmented with portable virtual reality equipment to engage participants in advocacy for changes. Participants (median age of 53 years) dedicated a median of 13.8 h a day to unpaid caregiving, had an average subjective well-being score of 7.0, and 19.1% and 23.8% reported having depression and generalized anxiety symptoms respectively. Caregivers reported that the program fosters their perception of purpose, enjoyment, resilience, and cognitive and emotional awareness. SOPARC evaluation showed that most women engaged in moderate to vigorous physical activity. The caregivers highlighted education, physical activity services, and integration of facilities as facilitators to accessing the Care Block program. Poor quality and lack of sidewalks and roads, limited personal safety, and the risk of pedestrian-vehicle collisions were identified as barriers. Virtual Reality sparked compelling dialogue between participants and stakeholders, allowing stakeholders to reflect on an urban program facilitating unpaid care work.

13.
Biochemistry (Mosc) ; 89(5): 942-957, 2024 May.
Article in English | MEDLINE | ID: mdl-38880654

ABSTRACT

Extensive skin damage requires specialized therapy that stimulates regeneration processes without scarring. The possibility of using combination of a collagen gel application as a wound dressing and fibroblast attractant with verteporfin as an antifibrotic agent was examined in vivo and in vitro. In vitro effects of verteporfin on viability and myofibroblast markers expression were evaluated using fibroblasts isolated from human scar tissue. In vivo the collagen gel and verteporfin (individually and in combination) were applied into the wound to investigate scarring during skin regeneration: deviations in skin layer thickness, collagen synthesis, and extracellular matrix fibers were characterized. The results indicate that verteporfin reduces fibrotic phenotype by suppressing expression of the contractile protein Sm22α without inducing cell death. However, administration of verteporfin in combination with the collagen gel disrupts its ability to direct wound healing in a scarless manner, which may be related to incompatibility of the mechanisms by which collagen and verteporfin control regeneration.


Subject(s)
Collagen , Fibroblasts , Verteporfin , Verteporfin/pharmacology , Verteporfin/therapeutic use , Humans , Collagen/metabolism , Fibroblasts/drug effects , Fibroblasts/metabolism , Animals , Wound Healing/drug effects , Antifibrotic Agents/pharmacology , Antifibrotic Agents/therapeutic use , Cells, Cultured , Tissue Scaffolds/chemistry , Cicatrix/drug therapy , Cicatrix/pathology , Cicatrix/metabolism , Male , Fibrosis , Skin/drug effects , Skin/pathology , Skin/metabolism
14.
Br J Sports Med ; 58(7): 359-365, 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38302280

ABSTRACT

OBJECTIVES: The objective was to investigate the benefits of the 'weekend warrior' physical activity pattern in Latin America, where many people take part in high levels of non-exercise physical activity. METHODS: Participants in the Mexico City Prospective Study were surveyed from 1998 to 2004 and resurveyed from 2015 to 2019. Those who exercised up to once or twice per week were termed weekend warriors. Those who exercised more often were termed regularly active. Analyses were adjusted for potential confounders. RESULTS: The main analysis included 26 006 deaths in 154 882 adults (67% female) aged 52±13 years followed for 18±4 years (mean±SD). Compared with those who reported no exercise, the HR (95% CI) was 0.88 (0.83 to 0.93) in the weekend warriors and 0.88 (0.84 to 0.91) in the regularly active. Similar results were observed for cardiovascular disease and cancer mortality, but associations were weaker. Stratified analyses showed that substantial reductions in all-cause mortality risk only occurred when the duration of exercise sessions was at least 30-60 min. The repeated-measures analysis included 843 deaths in 10 023 adults followed for 20±2 years. Compared with being inactive or becoming inactive, the HR was 0.86 (95% CI 0.65 to 1.12) when being a weekend warrior or becoming a weekend warrior and 0.85 (95% CI 0.70 to 1.03) when being regularly active or becoming regularly active. CONCLUSIONS: This is the first prospective study to investigate the benefits of the weekend warrior physical activity pattern in Latin America. The results suggest that even busy adults could benefit from taking part in one or two sessions of exercise per week.


Subject(s)
Cardiovascular Diseases , Neoplasms , Adult , Humans , Female , Male , Cardiovascular Diseases/prevention & control , Prospective Studies , Exercise , Mexico/epidemiology , Surveys and Questionnaires
15.
J Aging Phys Act ; 32(1): 91-106, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37883645

ABSTRACT

The community restrictions during the coronavirus disease 2019 pandemic adversely impacted older adults' physical activity levels. This convergent mixed-method study assessed the adaptation of the Recreovía, a community-based physical activity program in Bogotá, and characterized physical activity levels among older adult participants. Our results showed how the Recreovía adapted during the pandemic to continue promoting physical activity, through indoor and outdoor strategies, including virtual physical activity sessions and safety protocols. During this time, 72%-79% of the older adults attending the adapted program were physically active. A greater proportion of park users (84.2%) and more people involved in vigorous physical activity were observed during Recreovía days. Older adults had positive experiences and perceptions of the Recreovía program related to their health and social well-being. Even though the older adults prefer being outdoors, the adapted program allowed participants to continue with their physical activity routines as much as possible during the pandemic.


Subject(s)
COVID-19 , Humans , Aged , Colombia/epidemiology , COVID-19/prevention & control , Communicable Disease Control , Exercise
16.
Am J Epidemiol ; 192(12): 2006-2017, 2023 11 10.
Article in English | MEDLINE | ID: mdl-37420108

ABSTRACT

The Hispanic/Latino population experiences socioeconomic adversities across the lifespan and is at greater risk of cognitive impairment, yet little is known about the role of life-course socioeconomic position (SEP) in cognitive function in this population. Using baseline data (2008-2011) from adults (aged 45-74 years) of the Hispanic Community Health Study/Study of Latinos, we assessed the association between childhood SEP and socioeconomic mobility with cognitive function, and whether this association was mediated by midlife SEP. Childhood SEP was assessed using parental education. An index combining participants' education and household income represented midlife SEP. Socioeconomic mobility was categorized as stable low, downward or upward mobility, and stable high-SEP. Cognitive function measures were modeled using survey linear regression with inverse-probability weighting, accounting for covariates. We used mediation analysis to estimate the indirect effect of childhood SEP on cognition through midlife SEP. High childhood SEP was associated with global cognition in adulthood (coefficient for parental education beyond high school vs. less than high school = 0.26, 95% confidence interval: 0.15, 0.37). This association was partially mediated through midlife SEP (indirect effect coefficient = 0.16, 95% confidence interval: 0.15, 0.18). Low SEP through the life course was associated with the lowest cognitive function. This study provides evidence that life-course SEP influences cognitive performance in adulthood.


Subject(s)
Cognition , Hispanic or Latino , Socioeconomic Factors , Humans , Educational Status , Public Health , Risk Factors , Social Class , Middle Aged , Aged
17.
Annu Rev Public Health ; 44: 151-169, 2023 04 03.
Article in English | MEDLINE | ID: mdl-36525957

ABSTRACT

Given its origins in high-income countries, the field of physical activity and public health research and promotion has broadly followed a choice-based model. However, a substantial amount of the physical activity occurring routinely in many settings, particularly in low- and middle-income countries (LMICs), is the result of economic necessity and is not due to true, free choices. We propose the "necessity- versus choice-based physical activity models" framework as a conceptual tool to ground physical activity and public health research and promotion efforts in LMICs, helping ensurethat these efforts are relevant, ethical, responsive, and respectful to local contexts. Identifying ways to ensure that LMIC populations can maintain high levels of active transport while increasing opportunities for active leisure must be prioritized. To promote equity, physical activity research, programs, and policies in LMICs must focus on improving the conditions under which necessity-driven physical activity occurs for a vast majority of the population.


Subject(s)
Developing Countries , Exercise , Humans , Income , Public Health
18.
BMC Cancer ; 23(1): 398, 2023 May 04.
Article in English | MEDLINE | ID: mdl-37142955

ABSTRACT

BACKGROUND: To summarize recent evidence in terms of health-related quality of life (HRQoL), functional and oncological outcomes following radical prostatectomy (RP) compared to external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT) for high-risk prostate cancer (PCa). METHODS: We searched Medline, Embase, Cochrane Database of Systematic Reviews, Cochrane Controlled Trial Register and the International Standard Randomized Controlled Trial Number registry on 29 march 2021. Comparative studies, published since 2016, that reported on treatment with RP versus dose-escalated EBRT and ADT for high-risk non-metastatic PCa were included. The Newcastle-Ottawa Scale was used to appraise quality and risk of bias. A qualitative synthesis was performed. RESULTS: Nineteen studies, all non-randomized, met the inclusion criteria. Risk of bias assessment indicated low (n = 14) to moderate/high (n = 5) risk of bias. Only three studies reported functional outcomes and/or HRQoL using different measurement instruments and methods. A clinically meaningful difference in HRQoL was not observed. All studies reported oncological outcomes and survival was generally good (5-year survival rates > 90%). In the majority of studies, a statistically significant difference between both treatment groups was not observed, or only differences in biochemical recurrence-free survival were reported. CONCLUSIONS: Evidence clearly demonstrating superiority in terms of oncological outcomes of either RP or EBRT combined with ADT is lacking. Studies reporting functional outcomes and HRQoL are very scarce and the magnitude of the effect of RP versus dose-escalated EBRT with ADT on HRQoL and functional outcomes remains largely unknown.


Subject(s)
Androgen Antagonists , Prostatic Neoplasms , Humans , Male , Androgen Antagonists/therapeutic use , Androgens , Prostatectomy/methods , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/surgery , Quality of Life , Non-Randomized Controlled Trials as Topic
19.
Hum Genomics ; 16(1): 24, 2022 07 22.
Article in English | MEDLINE | ID: mdl-35869513

ABSTRACT

BACKGROUND: More than half of human protein-coding genes have an alternative transcription start site (TSS). We aimed to investigate the contribution of alternative TSSs to the acute-stress-induced transcriptome response in human tissue (skeletal muscle) using the cap analysis of gene expression approach. TSSs were examined at baseline and during recovery after acute stress (a cycling exercise). RESULTS: We identified 44,680 CAGE TSS clusters (including 3764 first defined) belonging to 12,268 genes and annotated for the first time 290 TSSs belonging to 163 genes. The transcriptome dynamically changes during the first hours after acute stress; the change in the expression of 10% of genes was associated with the activation of alternative TSSs, indicating differential TSSs usage. The majority of the alternative TSSs do not increase proteome complexity suggesting that the function of thousands of alternative TSSs is associated with the fine regulation of mRNA isoform expression from a gene due to the transcription factor-specific activation of various alternative TSSs. We identified individual muscle promoter regions for each TSS using muscle open chromatin data (ATAC-seq and DNase-seq). Then, using the positional weight matrix approach we predicted time course activation of "classic" transcription factors involved in response of skeletal muscle to contractile activity, as well as diversity of less/un-investigated factors. CONCLUSIONS: Transcriptome response induced by acute stress related to activation of the alternative TSSs indicates that differential TSSs usage is an essential mechanism of fine regulation of gene response to stress stimulus. A comprehensive resource of accurate TSSs and individual promoter regions for each TSS in muscle was created. This resource together with the positional weight matrix approach can be used to accurate prediction of TFs in any gene(s) of interest involved in the response to various stimuli, interventions or pathological conditions in human skeletal muscle.


Subject(s)
Gene Expression Regulation , Transcriptome , Humans , Muscle, Skeletal , Promoter Regions, Genetic/genetics , Transcription Initiation Site , Transcriptome/genetics
20.
Prev Med ; 177: 107720, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37802196

ABSTRACT

OBJECTIVE: We investigate the obesity transition at the country- and regional-levels, by age, gender, and socioeconomic status (SES) and its relationship to three health behavior attributes, including physical activity (PA), sedentary activities (ST), and consumption of ultra-processed foods (CUPF) within the urban population of Colombia, from 20,010 to 2050. METHODS: The study is informed by cross-sectional data from ENSIN survey. We used these data to develop a system dynamics model that simulates the dynamics of obesity by body mass index (BMI) categories, gender, and SES. This model also uses a conservative co-flow structure for three health-related behaviors (PA, ST, and CUPF). RESULTS: At the national level, our results indicate that the burden of obesity is shifting towards populations with lower SES as the gross domestic product (GDP) increases, particularly women aged 20-59 years with lower SES. Among this group of women, the highest burden of obesity is among those who do not meet the PA, ST and CUPF recommendations. At the regional level, our findings suggest that the regions are at different stages in the obesity transition. CONCLUSIONS: The burden of obesity is shifting towards women with lower SES as GDP increases at the national level and across several regions. This obesity transition is paralleled by a high prevalence of women from low SES groups who do not meet the minimum recommendations for PA, CUPF, and ST. Our findings can be used by decision-makers to inform age- and SES- specific policies seeking to tackle the obesity.


Subject(s)
Food, Processed , Sedentary Behavior , Humans , Female , Male , Colombia/epidemiology , Cross-Sectional Studies , Obesity/epidemiology , Body Mass Index , Exercise
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