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1.
Microbiol Spectr ; : e0004024, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38687120

RESUMO

The growth of pathogenic bacteria in moist and wet surfaces and tubing of medically relevant devices results in serious infections in immunocompromised patients. In this study, we investigated and demonstrated the successful implementation of a UV-C side-emitting optical fiber in disinfecting medically relevant pathogenic bacteria (Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus [MRSA]) within tight channels of polytetrafluoroethylene (PTFE). PTFE is a commonly used material both in point-of-use (POU) water treatment technologies and medical devices (dental unit water line [DUWL], endoscope). For a 1-m-long PTFE channel, up to ≥6 log inactivation was achieved using a 1-m-long UV side-emitting optical fiber (SEOF) with continuous 16-h exposure of low UV-C radiation ranging from ~0.23 to ~29.30 µW/cm2. Furthermore, a linear model was used to calculate the inhibition zone constant (k`), which enables us to establish a correlation between UV dosage and the extent of inactivated surface area (cm2) for surface-bound Escherichia coli on a nutrient-rich medium. The k` value for an irradiance ranging from ~150 to ~271.50 µW/cm2 was calculated to be 0.564 ± 0.6 cm·cm2/mJ. This study demonstrated the efficacy of SEOFs for disinfection of medically relevant microorganisms present in medically and domestically relevant tight channels. The impact of the results in this study extends to the optimization of operational efficiency in pre-existing UV surface disinfection setups that currently operate at UV dosages exceeding the optimal levels.IMPORTANCEGermicidal UV radiation has gained global recognition for its effectiveness in water and surface disinfection. Recently, various works have illustrated the benefit of using UV-C side-emitting optical fibers (SEOFs) for the disinfection of tight polytetrafluoroethylene (PTFE) channels. This study now demonstrates its impact for disinfection of medically relevant organisms and introduces critical design calculations needed for its implementation. The flexible geometry and controlled emission of light in these UV-SEOFs make them ideal for light distribution in tight channels. Moreover, the results presented in this manuscript provide a novel framework that can be employed in various applications, addressing microbial contamination and the disinfection of tight channels.

2.
J Clin Invest ; 134(6)2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38488000

RESUMO

Premature birth disrupts normal lung development and places infants at risk for bronchopulmonary dysplasia (BPD), a disease disrupting lung health throughout the life of an individual and that is increasing in incidence. The TGF-ß superfamily has been implicated in BPD pathogenesis, however, what cell lineage it impacts remains unclear. We show that TGFbr2 is critical for alveolar epithelial (AT1) cell fate maintenance and function. Loss of TGFbr2 in AT1 cells during late lung development leads to AT1-AT2 cell reprogramming and altered pulmonary architecture, which persists into adulthood. Restriction of fetal lung stretch and associated AT1 cell spreading through a model of oligohydramnios enhances AT1-AT2 reprogramming. Transcriptomic and proteomic analyses reveal the necessity of TGFbr2 expression in AT1 cells for extracellular matrix production. Moreover, TGF-ß signaling regulates integrin transcription to alter AT1 cell morphology, which further impacts ECM expression through changes in mechanotransduction. These data reveal the cell intrinsic necessity of TGF-ß signaling in maintaining AT1 cell fate and reveal this cell lineage as a major orchestrator of the alveolar matrisome.


Assuntos
Displasia Broncopulmonar , Alvéolos Pulmonares , Humanos , Camundongos , Animais , Recém-Nascido , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Alvéolos Pulmonares/metabolismo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Mecanotransdução Celular , Proteômica , Células Epiteliais Alveolares , Pulmão/patologia , Diferenciação Celular , Matriz Extracelular/metabolismo , Displasia Broncopulmonar/patologia , Transcrição Gênica
3.
Water Res ; 255: 121445, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38503182

RESUMO

Storm events play a crucial role in organic matter transport within watersheds and can increase the concentration and alter the composition of NOMs and DBP formation potential. To assess the impact that storm events can have on drinking water quality, samples were collected and analyzed across four storm events in the Neversink River, Catskill region, New York in 2019 and 2022. Source water natural organic matter (NOM) was characterized, and the change of NOM quality was evaluated due to storm impacts. During storm events, a high level of NOM mobilization is initiated by heavy precipitation causing overland flow and a rise in the water table. In this way, storms result in increased access to stored NOM pools that are generated during inter-storm periods. A significant correlation was observed between several organic water quality parameters such as UV absorbance (UV254), dissolved organic carbon (DOC) and chlorine demand. Precursors for the total trihalomethanes (TTHM), dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) exhibited comparable patterns with UV254, DOC, and chlorine demand for four storms. Despite the potential for increased dilution resulting from higher discharges, all organic water quality parameters, including yields of disinfection byproducts (i.e., DBP precursors), exhibited elevated concentrations during periods of higher flows. Three of the four storms showed hysteresis patterns with higher observed concentrations of organic constituents in the falling limb of the hydrographs. Precursors for the nitrogenous DBPs (N-DBPs) were proportional to the DOC for all four storms. The coefficient of determination (R2) for TTHM, DCAA, TCAA with UV254 is higher (R2 0.92-0.98) than corresponding correlations with DOC (R2 0.89-0.92). The R2 for UV254 showed the following hierarchy: DCAA≈TCAA>TTHM. Additionally, the R2 for DOC and specific ultraviolet absorbance (SUVA) had the following hierarchy: DCAA>TCAA>TTHM and TCAA>DCAA>TTHM respectively. A significant correlation between UV254 and DOC (R = 0.99) for all storms was observed. Chlorine demand also yielded a strong correlation (R = 0.91∼0.98) with UV254 and DOC. This research indicates that a significant and disproportionate export of NOM to source waters occurs during storm events compared to baseflow conditions. Consequently, it is recommended for drinking water treatment facilities to reassess chlorine dosages during these events. Treatment plants can employ UV254 as a tool to determine appropriate chlorine dosages, aiming to mitigate DBP formation in treated waters.

4.
Biofilm ; 7: 100186, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38495771

RESUMO

Marine biofouling causes serious environmental problems and has adverse impacts on the maritime industry. Biofouling on windows and optical equipment reduces surface transparency, limiting their application for on-site monitoring or continuous measurement. This work illustrates that UV emitting glasses (UEGs) can prevent the establishment and growth of biofilm on the illuminated surfaces. Specifically, this paper describes how UEGs are enabled by innovatively modifying the surfaces of the glass with light scattering particles. Modification of glass surface with silica nanoparticles at a concentration 26.5 µg/cm2 resulted in over ten-fold increase in UV irradiance, while maintaining satisfactory visible and IR transparency metrics of over 99 %. The UEG reduced visible biological growth by 98 % and resulted in a decrease of 1.79 log in detected colony forming units when compared to the control during a 20 day submersion at Port Canaveral, Florida, United States. These findings serve as strong evidence that UV emitting glass should be explored as a promising approach for biofilm inhibition on transparent surfaces.

5.
Nat Metab ; 6(4): 697-707, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38413806

RESUMO

Post-translational modifications (PTMs) on histones are a key source of regulation on chromatin through impacting cellular processes, including gene expression1. These PTMs often arise from metabolites and are thus impacted by metabolism and environmental cues2-7. One class of metabolically regulated PTMs are histone acylations, which include histone acetylation, butyrylation, crotonylation and propionylation3,8. As these PTMs can be derived from short-chain fatty acids, which are generated by the commensal microbiota in the intestinal lumen9-11, we aimed to define how microbes impact the host intestinal chromatin landscape, mainly in female mice. Here we show that in addition to acetylation, intestinal epithelial cells from the caecum and distal mouse intestine also harbour high levels of butyrylation and propionylation on lysines 9 and 27 of histone H3. We demonstrate that these acylations are regulated by the microbiota and that histone butyrylation is additionally regulated by the metabolite tributyrin. Tributyrin-regulated gene programmes are correlated with histone butyrylation, which is associated with active gene-regulatory elements and levels of gene expression. Together, our study uncovers a regulatory layer of how the microbiota and metabolites influence the intestinal epithelium through chromatin, demonstrating a physiological setting in which histone acylations are dynamically regulated and associated with gene regulation.


Assuntos
Microbioma Gastrointestinal , Regulação da Expressão Gênica , Histonas , Processamento de Proteína Pós-Traducional , Animais , Histonas/metabolismo , Camundongos , Feminino , Mucosa Intestinal/metabolismo , Acetilação , Intestinos/microbiologia , Triglicerídeos/metabolismo , Camundongos Endogâmicos C57BL
6.
Biomolecules ; 14(1)2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38254724

RESUMO

Organisms are often subjected to conditions that promote cellular stress. Cell responses to stress include the activation of pathways to defend against and recover from the stress, or the initiation of programmed cell death to eliminate the damaged cells. One of the processes that can be triggered under stress is the transcription and variation in the number of copies of satellite DNA sequences (satDNA), which are involved in response mechanisms. Satellite DNAs are highly repetitive tandem sequences, mainly located in the centromeric and pericentromeric regions of eukaryotic chromosomes, where they form the constitutive heterochromatin. Satellite non-coding RNAs (satncRNAs) are important regulators of cell processes, and their deregulation has been associated with disease. Also, these transcripts have been associated with stress-response mechanisms in varied eukaryotic species. This review intends to explore the role of satncRNAs when cells are subjected to adverse conditions. Studying satDNA transcription under various stress conditions and deepening our understanding of where and how these sequences are involved could be a key factor in uncovering important facts about the functions of these sequences.


Assuntos
Apoptose , Cognição
7.
Circulation ; 149(9): 644-655, 2024 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-37883682

RESUMO

BACKGROUND: The optimal treatment in patients with severe aortic stenosis and small aortic annulus (SAA) remains to be determined. This study aimed to compare the hemodynamic and clinical outcomes between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in patients with a SAA. METHODS: This prospective multicenter international randomized trial was performed in 15 university hospitals. Participants were 151 patients with severe aortic stenosis and SAA (mean diameter <23 mm) randomized (1:1) to TAVR (n=77) versus SAVR (n=74). The primary outcome was impaired valve hemodynamics (ie, severe prosthesis patient mismatch or moderate-severe aortic regurgitation) at 60 days as evaluated by Doppler echocardiography and analyzed in a central echocardiography core laboratory. Clinical events were secondary outcomes. RESULTS: The mean age of the participants was 75.5±5.1 years, with 140 (93%) women, a median Society of Thoracic Surgeons predicted risk of mortality of 2.50% (interquartile range, 1.67%-3.28%), and a median annulus diameter of 21.1 mm (interquartile range, 20.4-22.0 mm). There were no differences between groups in the rate of severe prosthesis patient mismatch (TAVR, 4 [5.6%]; SAVR, 7 [10.3%]; P=0.30) and moderate-severe aortic regurgitation (none in both groups). No differences were found between groups in mortality rate (TAVR, 1 [1.3%]; SAVR, 1 [1.4%]; P=1.00) and stroke (TAVR, 0; SAVR, 2 [2.7%]; P=0.24) at 30 days. After a median follow-up of 2 (interquartile range, 1-4) years, there were no differences between groups in mortality rate (TAVR, 7 [9.1%]; SAVR, 6 [8.1%]; P=0.89), stroke (TAVR, 3 [3.9%]; SAVR, 3 [4.1%]; P=0.95), and cardiac hospitalization (TAVR, 15 [19.5%]; SAVR, 15 [20.3%]; P=0.80). CONCLUSIONS: In patients with severe aortic stenosis and SAA (women in the majority), there was no evidence of superiority of contemporary TAVR versus SAVR in valve hemodynamic results. After a median follow-up of 2 years, there were no differences in clinical outcomes between groups. These findings suggest that the 2 therapies represent a valid alternative for treating patients with severe aortic stenosis and SAA, and treatment selection should likely be individualized according to baseline characteristics, additional anatomical risk factors, and patient preference. However, the results of this study should be interpreted with caution because of the limited sample size leading to an underpowered study, and need to be confirmed in future larger studies. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03383445.


Assuntos
Insuficiência da Valva Aórtica , Estenose da Valva Aórtica , Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Acidente Vascular Cerebral , Substituição da Valva Aórtica Transcateter , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/cirurgia , Insuficiência da Valva Aórtica/etiologia , Estudos Prospectivos , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Resultado do Tratamento , Substituição da Valva Aórtica Transcateter/efeitos adversos , Fatores de Risco , Acidente Vascular Cerebral/etiologia
9.
BMC Public Health ; 23(1): 2454, 2023 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-38062435

RESUMO

BACKGROUND: Changes in food environments have the potential to affect consumption, nutritional status, and health, and understanding these changes is of utmost importance. This study, therefore, aimed to examine the fluctuation of food stores that sell fruits and vegetables over five years in the health promotion service area of Primary Health Care (PHC) in Belo Horizonte, Minas Gerais, Brazil. METHODS: This was an ecological study that used data from a food environment audit conducted in the realm of Brazilian PHC. Buffers of 1 mile (equivalent to 1600 m) were created around health promotion services to define food environments. All food stores and open-air food markets that sold fruits and vegetables (FV) within this buffer area were considered eligible. The data collection was performed during two periods: the baseline, in 2013, and after five years, in 2018. This study compares the fluctuation by the type of stores and according to the health vulnerability index (HVI). RESULTS: After 5 years, 35.2% of the stores were stable; 154 stores were closed, and 155 were opened. The stability was greater in low-vulnerability areas, and the fluctuation differed by type of store only for areas with high vulnerability. The number of supermarket decreased in high HVI territories; and local stores, showed greater stability when compared to specialized FV markets. CONCLUSIONS: The differences in store fluctuations according to the vulnerability of areas demonstrate the importance of food supply policies considering the local characteristics to reduce inequities of access to healthy foods.


Assuntos
Comércio , Características de Residência , Humanos , Brasil , Frutas , Verduras , Abastecimento de Alimentos
10.
Prev Med ; 177: 107748, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37913915

RESUMO

OBJECTIVE: To assess longitudinal effects of a nutrition intervention on fruit and vegetable (F&V) intake among Primary Health Care (PHC) service participants in Belo Horizonte, Brazil. METHODS: Demographics and health data on 3414 PHC service participants were collected at baseline in 2013-2014. F&V intake was assessed at baseline, 12, 36, and 48 months until 2017-2018. Services were randomized to control (CG, usual care) or intervention (IG, usual care and a Transtheoretical Model-based intervention to increase F&V intake). We performed difference-in-differences (DiD) analysis to identify intervention effects on F&V intake, and sensitivity analyses of participants observed at all timepoints. RESULTS: Participants were mostly middle-aged, low-income women. Mean baseline intakes were 168.7 g of fruit, 202.0 g of vegetables, and 370.7 g of F&V, with lower fruit in the IG (164.1 g) than the CG (172.3 g). At 12 months, the intervention increased fruit intake in the IG and fruit and F&V intake among individuals with low baseline F&V intake. Fruit intake remained higher at 36 months in the IG. No effect on vegetable intake was identified. According to sensitivity analyses, effects on fruit intake among the complete sample did not remain significant at 36 months, and an effect on fruit intake at 36 months was identified among those with adequate baseline F&V intake. Reductions in F&V intake did not remain significant. CONCLUSIONS: At 12 months, a TTM-based intervention increased fruit intake in the overall sample, and fruit and F&V intake among individuals with low baseline intakes. Repeated interventions may be needed over time. TRIAL REGISTRATION NUMBER: RBR-9h7ckx.


Assuntos
Frutas , Verduras , Feminino , Humanos , Pessoa de Meia-Idade , Brasil , Dieta , Comportamento Alimentar , Seguimentos , Promoção da Saúde , Masculino
11.
J Cell Sci ; 136(22)2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37921359

RESUMO

The nucleolus is sensitive to stress and can orchestrate a chain of cellular events in response to stress signals. Despite being a growth factor, FGF2 has antiproliferative and tumor-suppressive functions in some cellular contexts. In this work, we investigated how the antiproliferative effect of FGF2 modulates chromatin-, nucleolus- and rDNA-associated proteins. The chromatin and nucleolar proteome indicated that FGF2 stimulation modulates proteins related to transcription, rRNA expression and chromatin-remodeling proteins. The global transcriptional rate and nucleolus area increased along with nucleolar disorganization upon 24 h of FGF2 stimulation. FGF2 stimulation induced immature rRNA accumulation by increasing rRNA transcription. The rDNA-associated protein analysis reinforced that FGF2 stimulus interferes with transcription and rRNA processing. RNA Pol I inhibition partially reversed the growth arrest induced by FGF2, indicating that changes in rRNA expression might be crucial for triggering the antiproliferative effect. Taken together, we demonstrate that the antiproliferative FGF2 stimulus triggers significant transcriptional changes and modulates the main cell transcription site, the nucleolus.


Assuntos
Nucléolo Celular , Fator 2 de Crescimento de Fibroblastos , Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/farmacologia , Fator 2 de Crescimento de Fibroblastos/metabolismo , Nucléolo Celular/metabolismo , RNA Ribossômico/genética , RNA Ribossômico/metabolismo , Transcrição Gênica , DNA Ribossômico/genética , Cromatina/genética , Cromatina/metabolismo
12.
PLoS One ; 18(9): e0291609, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37733703

RESUMO

OBJECTIVE: This study analyzes the effect of the Brazilian National Oral Health Policy (NOHP) on oral cancer mortality rates (OCMR). METHOD: This is an ecological study with secondary oral cancer death data, using interrupted time series analysis (ARIMA, Autoregressive Integrated Moving Average). Annual death data were collected from the Mortality Information System (1996-2019). The outcome was the OCMR, standardized by gender and age We considered the NOHP, categorized as "0" (before its implementation), from 1996 to 2004, and "1 to 15", from 2005 to 2019. ARIMA modeling was carried out for temporal analysis, and regression coefficient estimation (RC). RESULTS: The Brazilian NOHP implementation was associated with an increase in OCMR in the North region (CR = 0.16; p = 0.022) and with a decrease in the Southeast region (CR = -0.04; p<0.001), but did not affect the other macro-regions nor Brazil. The forecast models estimated an increase in OCMR for the North, and Northeast, a decrease for the Southeast, and stability for the South and Brazil. CONCLUSION: The Brazilian NOHP is not being effective in reducing the OCMR. The trends behaved differently in the Brazilian territory, highlighting health inequities. We recommend that the NOHP strengthen the oral health care network, incorporating oral cancer as a notifiable disease, adopting strategies for prevention, screening, and providing opportunities for early treatment of the disease.


Assuntos
Neoplasias Bucais , Segunda Neoplasia Primária , Humanos , Brasil/epidemiologia , Desigualdades de Saúde , Análise de Séries Temporais Interrompida
13.
Front Cardiovasc Med ; 10: 1182530, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37727304

RESUMO

B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-pro BNP) are cardiac biomarkers that are released in response to increased ventricular and atrial wall stress. Aortic stenosis (AS) leads to hemodynamic changes and left ventricular hypertrophy and may be associated with natriuretic peptide levels. Several studies have shown that increased natriuretic peptide levels are correlated with AS severity and can predict the need for intervention. It can be useful in risk stratification, monitoring follow-up, and predicting cardiovascular outcomes of patients with severe AS. This paper aims to summarize the evidence of the role of BNP and NT-pro BNP in AS, before and after intervention.

14.
J Fungi (Basel) ; 9(8)2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37623619

RESUMO

Austropuccinia psidii is a biotrophic fungus that causes myrtle rust. First described in Brazil, it has since spread to become a globally important pathogen that infects more than 480 myrtaceous species. One of the most important commercial crops affected by A. psidii is eucalypt, a widely grown forestry tree. The A. psidii-Eucalyptus spp. interaction is poorly understood, but pathogenesis is likely driven by pathogen-secreted effector molecules. Here, we identified and characterized a total of 255 virulence effector candidates using a genome assembly of A. psidii strain MF-1, which was recovered from Eucalyptus grandis in Brazil. We show that the expression of seven effector candidate genes is modulated by cell wax from leaves sourced from resistant and susceptible hosts. Two effector candidates with different subcellular localization predictions, and with specific gene expression profiles, were transiently expressed with GFP-fusions in Nicotiana benthamiana leaves. Interestingly, we observed the accumulation of an effector candidate, Ap28303, which was upregulated under cell wax from rust susceptible E. grandis and described as a peptidase inhibitor I9 domain-containing protein in the nucleus. This was in accordance with in silico analyses. Few studies have characterized nuclear effectors. Our findings open new perspectives on the study of A. psidii-Eucalyptus interactions by providing a potential entry point to understand how the pathogen manipulates its hosts in modulating physiology, structure, or function with effector proteins.

16.
Artigo em Inglês | MEDLINE | ID: mdl-37444114

RESUMO

To evaluate the effectiveness of a collective intervention to encourage the consumption of fruits and vegetables on the nutrients intake for the prevention of chronic non-communicable diseases (NCDs), a randomized controlled community trial was conducted with a representative sample from the Health Academy Program. While the individuals in the control group (CG) participated in regular physical exercise, those in the intervention group (IG) also participated in a collective intervention. After 12 months, IG and CG showed a reduction in energy, omega 3 and sodium intake and an increase in the consumption of carbohydrates, fiber, vitamins, and minerals. Individuals from the CG showed an increase in phosphorus consumption and, in the IG, a reduction in the consumption of total, saturated, and polyunsaturated fats as well as an increase in the consumption of monounsaturated fats was seen. In both groups, there was an increase in the prevalence of adequate nutrients. Participation in the nutritional intervention was associated with lower consumption of energy and protein in the diet. The results pointed to the importance of individuals' participation in the program, which, associated with nutritional intervention, promoted an improvement in the nutrient profile of the diet and the prevention and control of NCDs.


Assuntos
Frutas , Verduras , Humanos , Gorduras na Dieta , Dieta , Nutrientes , Promoção da Saúde , Doença Crônica
17.
Materials (Basel) ; 16(12)2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37374666

RESUMO

Tissue regeneration of large bone defects is still a clinical challenge. Bone tissue engineering employs biomimetic strategies to produce graft composite scaffolds that resemble the bone extracellular matrix to guide and promote osteogenic differentiation of the host precursor cells. Aerogel-based bone scaffold preparation methods have been increasingly improved to overcome the difficulties in balancing the need for an open highly porous and hierarchically organized microstructure with compression resistance to withstand bone physiological loads, especially in wet conditions. Moreover, these improved aerogel scaffolds have been implanted in vivo in critical bone defects, in order to test their bone regeneration potential. This review addresses recently published studies on aerogel composite (organic/inorganic)-based scaffolds, having in mind the various cutting-edge technologies and raw biomaterials used, as well as the improvements that are still a challenge in terms of their relevant properties. Finally, the lack of 3D in vitro models of bone tissue for regeneration studies is emphasized, as well as the need for further developments to overcome and minimize the requirement for studies using in vivo animal models.

18.
Front Cardiovasc Med ; 10: 1197408, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37378406

RESUMO

Introduction: Classical low-flow, low-gradient aortic stenosis (LFLG-AS) is an advanced stage of aortic stenosis, which has a poor prognosis with medical treatment and a high operative mortality after surgical aortic valve replacement (SAVR). There is currently a paucity of information regarding the current prognosis of classical LFLG-AS patients undergoing SAVR and the lack of a reliable risk assessment tool for this particular subset of AS patients. The present study aims to assess mortality predictors in a population of classical LFLG-AS patients undergoing SAVR. Methods: This is a prospective study including 41 consecutive classical LFLG-AS patients (aortic valve area ≤1.0 cm2, mean transaortic gradient <40 mmHg, left ventricular ejection fraction <50%). All patients underwent dobutamine stress echocardiography (DSE), 3D echocardiography, and T1 mapping cardiac magnetic resonance (CMR). Patients with pseudo-severe aortic stenosis were excluded. Patients were divided into groups according to the median value of the mean transaortic gradient (≤25 and >25 mmHg). All-cause, intraprocedural, 30-day, and 1-year mortality rates were evaluated. Results: All of the patients had degenerative aortic stenosis, with a median age of 66 (60-73) years; most of the patients were men (83%). The median EuroSCORE II was 2.19% (1.5%-4.78%), and the median STS was 2.19% (1.6%-3.99%). On DSE, 73.2% had flow reserve (FR), i.e., an increase in stroke volume ≥20% during DSE, with no significant differences between groups. On CMR, late gadolinium enhancement mass was lower in the group with mean transaortic gradient >25 mmHg [2.0 (0.0-8.9) g vs. 8.5 (2.3-15.0) g; p = 0.034), and myocardium extracellular volume (ECV) and indexed ECV were similar between groups. The 30-day and 1-year mortality rates were 14.6% and 43.8%, respectively. The median follow-up was 4.1 (0.3-5.1) years. By multivariate analysis adjusted for FR, only the mean transaortic gradient was an independent predictor of mortality (hazard ratio: 0.923, 95% confidence interval: 0.864-0.986, p = 0.019). A mean transaortic gradient ≤25 mmHg was associated with higher all-cause mortality rates (log-rank p = 0.038), while there was no difference in mortality regarding FR status (log-rank p = 0.114). Conclusions: In patients with classical LFLG-AS undergoing SAVR, the mean transaortic gradient was the only independent mortality predictor in patients with LFLG-AS, especially if ≤25 mmHg. The absence of left ventricular FR had no prognostic impact on long-term outcomes.

19.
bioRxiv ; 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37214932

RESUMO

Premature birth disrupts normal lung development and places infants at risk for bronchopulmonary dysplasia (BPD), a disease increasing in incidence which disrupts lung health throughout the lifespan. The TGFß superfamily has been implicated in BPD pathogenesis, however, what cell lineage it impacts remains unclear. We show that Tgfbr2 is critical for AT1 cell fate maintenance and function. Loss of Tgfbr2 in AT1 cells during late lung development leads to AT1-AT2 cell reprogramming and altered pulmonary architecture, which persists into adulthood. Restriction of fetal lung stretch and associated AT1 cell spreading through a model of oligohydramnios enhances AT1-AT2 reprogramming. Transcriptomic and proteomic analysis reveal the necessity of Tgfbr2 expression in AT1 cells for extracellular matrix production. Moreover, TGFß signaling regulates integrin transcription to alter AT1 cell morphology, which further impacts ECM expression through changes in mechanotransduction. These data reveal the cell intrinsic necessity of TGFß signaling in maintaining AT1 cell fate and reveal this cell lineage as a major orchestrator of the alveolar matrisome.

20.
J Nutr ; 153(5): 1309-1322, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36934952

RESUMO

BACKGROUND: Eating disorders (EDs) compromise individuals' nutritional status, affecting, among other organs and systems, bone health. OBJECTIVES: This study aimed to assess and compare bone mineral density (BMD) from DXA scan and deuterium (D2O) dilution of adult females with anorexia nervosa (AN) and bulimia nervosa (BN). METHODS: This was a cross-sectional study with 53 female participants (18-49 y) with a diagnosis of AN (n = 25) or BN (n = 28). DXA scan was performed to assess BMD, FM, and FFM, and D2O dilution was used to assess total body water (TBW), FM, and FFM. Interviews/questionnaires were used to assess symptoms, illness trajectory, and physical activity. t-test, chi-square test, Pearson's linear correlation, linear regressions, and Bland-Altman analyses were performed, with a significance level of 5%. RESULTS: TBW below the recommended level for adult females (≥ 45%) was more frequent in BN (60%) compared with AN (21%; P = 0.013). FM index (FMI) (soft tissue only) (t-test P = 0.06), and FFM index (FFMI) (t-test P = 0.08) agreed between DXA scan and D2O dilution. Only FFMI did not show systematic bias of proportion (ß: -0.2, P = 0.177). The diagnosis of BN, binge-eating episodes, and physical activity in AN were associated with the differences in the methods' results. FMI was positively associated with BMD in AN, and both FMI and FFMI were positively associated with BMD in BN. CONCLUSIONS: In adult females with EDs, DXA scan and D2O dilution achieved agreement for FMI and FFMI. Changes in FM and FFM are important in understanding the mechanisms behind bone loss in EDs. Protocols for body composition assessment in EDs can help to minimize the effect of the ED diagnosis, ED behaviors (that is, excessive exercise and purging behaviors), and weight on the accuracy of measurements.


Assuntos
Anorexia Nervosa , Bulimia Nervosa , Humanos , Adulto , Feminino , Absorciometria de Fóton/métodos , Deutério , Estudos Transversais , Composição Corporal
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