Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 1.248
Filter
1.
Article in English | LILACS-Express | LILACS | ID: biblio-1565200

ABSTRACT

ABSTRACT Objective: To evaluate the seasonality of acute bronchiolitis in Brazil during the 2020-2022 season and compare it with the previous seasons. Methods: Data from the incidence of hospitalizations due to acute bronchiolitis in infants <1 year of age were obtained from the Department of Informatics of the Brazilian Public Health database for the period between 2016 and 2022. These data were also analyzed by macro-regions of Brazil (North, Northeast, Southeast, South, and Midwest). To describe seasonal and trend characteristics over time, we used the Seasonal Autoregressive Integrated Moving Averages Model. Results: Compared to the pre-COVID-19 period, the incidence of hospitalizations related to acute bronchiolitis decreased by 97% during non-pharmacological interventions (March 2020 - August 2021) but increased by 95% after non-pharmacological interventions relaxation (September 2021 - December 2022), resulting in a 16% overall increase. During the pre-COVID-19 period, hospitalizations for acute bronchiolitis followed a seasonal pattern, which was disrupted in 2020-2021 but recovered in 2022, with a peak occurring in May, approximately 4% higher than the pre-COVID-19 peak. Conclusions: This study underscores the significant influence of COVID-19 interventions on acute bronchiolitis hospitalizations in Brazil. The restoration of a seasonal pattern in 2022 highlights the interplay between public health measures and respiratory illness dynamics in young children.


RESUMO Objetivo: Avaliar a sazonalidade da bronquiolite aguda no Brasil durante a temporada 2020-2022 e compará-la com a das temporadas anteriores. Métodos: Os dados de incidência de internações por bronquiolite aguda em lactentes <1 ano de idade foram obtidos do Departamento de Informática da base de dados da Saúde Pública Brasileira para o período entre 2016 e 2022. Esses dados também foram analisados por macrorregiões do Brasil (Norte, Nordeste, Sudeste, Sul e Centro-Oeste). Para descrever características sazonais e de tendência ao longo do tempo, utilizamos o Modelo de Médias Móveis Integradas Autorregressivas Sazonais. Resultados: Em comparação com o período pré-COVID-19, a incidência de hospitalizações relacionadas com bronquiolite aguda diminuiu 97% durante as intervenções não farmacológicas (março de 2020 - agosto de 2021), mas aumentou 95% após a flexibilização das intervenções não farmacológicas (setembro de 2021 - dezembro de 2022), resultando no aumento geral de 16%. Durante o período pré-COVID-19, as hospitalizações por bronquiolite aguda seguiram um padrão sazonal, que foi interrompido em 2020-2021, mas recuperaram-se em 2022, com um pico ocorrido em maio, aproximadamente 4% superior ao pico pré-COVID-19. Conclusões: Este estudo ressalta a influência significativa das intervenções contra a COVID-19 nas hospitalizações por bronquiolite aguda no Brasil. A restauração de um padrão sazonal em 2022 sublinha a interação entre as medidas de saúde pública e a dinâmica das doenças respiratórias em crianças pequenas.

2.
Andes Pediatr ; 95(3): 272-278, 2024 Jun.
Article in Spanish | MEDLINE | ID: mdl-39093212

ABSTRACT

Up to 80% of children admitted to a hospital experience pain, mainly associated with venipuncture. OBJECTIVE: To analyze whether the use of virtual reality (VR) headsets during venipuncture can modify the perception of pain, anxiety, and fear in pediatrics. PATIENTS AND METHOD: Open label, randomized clinical trial. The presence of intellectual, visual, or hearing impairment were considered exclusion criteria. Two anxiety and fear scales were administered before and after the procedure, and the Wong-Baker face pain scale at the end. The following were recorded: number of venipuncture attempts, duration of the procedure, and side effects. RESULTS: 78 patients were included, 38 males and a mean age of 9.63 years. In the intervention group, the mean pain value was 2.87, with a mean difference (MD) of -0.85 compared with the control one (95% confidence interval (CI) -2.02 to 0.33). There was a significant reduction in the level of anxiety and fear, with MDs of -2.59 (95%CI: -3.92 to -1.26) and -0.85 points (95%CI: -1.45 to -0.24), respectively. CONCLUSIONS: the use of VR headsets in venipuncture in hospital daytime care decreases the level of anxiety and fear in children and seems to reduce pain, without adverse effects. The venipuncture procedure has the same success rate and does not increase its duration.


Subject(s)
Anxiety , Fear , Pain Measurement , Phlebotomy , Virtual Reality , Humans , Male , Fear/psychology , Phlebotomy/adverse effects , Phlebotomy/psychology , Female , Anxiety/prevention & control , Child , Adolescent , Pain, Procedural/prevention & control , Pain, Procedural/etiology , Pain/prevention & control , Pain/psychology , Outpatients , Virtual Reality Exposure Therapy/methods , Child, Preschool
3.
Microb Biotechnol ; 17(8): e14543, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39096350

ABSTRACT

Arguably, the greatest threat to bacteria is phages. It is often assumed that those bacteria that escape phage infection have mutated or utilized phage-defence systems; however, another possibility is that a subpopulation forms the dormant persister state in a manner similar to that demonstrated for bacterial cells undergoing nutritive, oxidative, and antibiotic stress. Persister cells do not undergo mutation and survive lethal conditions by ceasing growth transiently. Slower growth and dormancy play a key physiological role as they allow host phage defence systems more time to clear the phage infection. Here, we investigated how bacteria survive lytic phage infection by isolating surviving cells from the plaques of T2, T4, and lambda (cI mutant) virulent phages and sequencing their genomes. We found that bacteria in plaques can escape phage attack both by mutation (i.e. become resistant) and without mutation (i.e. become persistent). Specifically, whereas T4-resistant and lambda-resistant bacteria with over a 100,000-fold less sensitivity were isolated from plaques with obvious genetic mutations (e.g. causing mucoidy), cells were also found after T2 infection that undergo no significant mutation, retain wild-type phage sensitivity, and survive lethal doses of antibiotics. Corroborating this, adding T2 phage to persister cells resulted in 137,000-fold more survival compared to that of addition to exponentially growing cells. Furthermore, our results seem general in that phage treatments with Klebsiella pneumonia and Pseudomonas aeruginosa also generated persister cells. Hence, along with resistant strains, bacteria also form persister cells during phage infection.


Subject(s)
Bacteriophages , Bacteriophages/genetics , Bacteriophages/physiology , Microbial Viability/drug effects , Mutation , Bacteria/virology , Bacteria/genetics , Bacteria/drug effects , Genome, Viral , Pseudomonas aeruginosa/virology , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/genetics
4.
BMC Pulm Med ; 24(1): 334, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38987754

ABSTRACT

BACKGROUND: Risk scores (RS) evaluate the likelihood of short-term mortality in patients diagnosed with community-acquired pneumonia (CAP). However, there is a scarcity of evidence to determine the risk of long-term mortality. This article aims to compare the effectiveness of 16 scores in predicting mortality at three, six, and twelve months in adult patients with CAP. METHODS: A retrospective cohort study on individuals diagnosed with CAP was conducted across two hospitals in Colombia. Receiver Operating Characteristic (ROC) curves were constructed at 3, 6, and 12 months to assess the predictive ability of death for the following scoring systems: CURB-65, CRB-65, SCAP, CORB, ADROP, NEWS, Pneumonia Shock, REA-ICU, PSI, SMART-COP, SMRT-CO, SOAR, qSOFA, SIRS, CAPSI, and Charlson Comorbidity Index (CCI). RESULTS: A total of 3688 patients were included in the final analysis. Mortality at 3, 6, and 12 months was 5.2%, 8.3%, and 16.3% respectively. At 3 months, PSI, CCI, and CRB-65 scores showed ROC curves of 0.74 (95% CI: 0.71-0.77), 0.71 (95% CI: 0.67-0.74), and 0.70 (95% CI: 0.66-0.74). At 6 months, PSI and CCI scores showed performances of 0.74 (95% CI: 0.72-0.77) and 0.72 (95% CI: 0.69-0.74), respectively. Finally at 12 months, all evaluated scores showed poor discriminatory capacity, including PSI, which decreased from acceptable to poor with an ROC curve of 0.64 (95% CI: 0.61-0.66). CONCLUSION: When predicting mortality in patients with CAP, at 3 months, PSI, CCI, and CRB-65 showed acceptable predictive performances. At 6 months, only PSI and CCI maintained acceptable levels of accuracy. For the 12-month period, all evaluated scores exhibited very limited discriminatory ability, ranging from poor to almost negligible.


Subject(s)
Community-Acquired Infections , Pneumonia , ROC Curve , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Colombia/epidemiology , Community-Acquired Infections/mortality , Community-Acquired Infections/diagnosis , Pneumonia/mortality , Pneumonia/diagnosis , Prognosis , Retrospective Studies , Risk Assessment/methods , Severity of Illness Index , Time Factors
5.
RMD Open ; 10(2)2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39043441

ABSTRACT

OBJECTIVE: To evaluate cognitive function in patients with rheumatoid arthritis (RA) and inflammatory activity. PATIENTS AND METHODS: We performed a cross-sectional study of a cohort of patients with RA initiating their first biological treatment due to moderate-to-high inflammation and a healthy control group (no inflammatory diseases) matched for age, sex and educational level. All participants underwent a comprehensive neuropsychological assessment, with cognitive impairment defined as a Montreal Cognitive Assessment (MoCA) score<26. Additional assessments included various cognitive tests (STROOP, forward and backward digit spans), anxiety and depression scales (Hospital Anxiety and Depression Scale), quality of life measures (Quality of Life-Rheumatoid Arthritis) and average inflammatory activity according to the 28-joint Disease Activity Score (DAS28)-C-reactive protein (CRP) into high activity (DAS28≥3.2) and low activity (DAS28<3.2) groups, also CRP levels and interleukin 6 (IL-6) levels were measured using an ELISA. RESULTS: The study population comprised 140 participants, 70 patients with RA and 70 controls. Patients more frequently experienced cognitive impairment than controls (60% vs 40%; p=0.019) and had lower mean (SD) values in the MoCA (23.6 (3.9) vs 25.1 (3.4); p=0.019. As for subtests of the MoCA, involvement was more marked in patients than in controls for the visuospatial-executive (p=0.030), memory (p=0.026) and abstraction (p=0.039) domains. Additionally, patients scored lower on executive function, as assessed by the backward digit span test (4.0 (1.7) vs 4.7 (1.9); p=0.039). Cognitive impairment is associated with age and a lower educational level in the general population, and among patients with RA with educational level, obesity and average inflammatory activity (DAS28, CRP, and IL-6). CONCLUSIONS: Patients with RA with high inflammatory activity are more susceptible to cognitive impairment, which specifically affects the domains of visuospatial, memory, abstraction and executive function.


Subject(s)
Arthritis, Rheumatoid , C-Reactive Protein , Cognition , Cognitive Dysfunction , Inflammation , Neuropsychological Tests , Humans , Arthritis, Rheumatoid/psychology , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/blood , Male , Female , Middle Aged , Cross-Sectional Studies , Inflammation/blood , Inflammation/etiology , C-Reactive Protein/metabolism , C-Reactive Protein/analysis , Cognitive Dysfunction/etiology , Cognitive Dysfunction/diagnosis , Aged , Quality of Life , Biomarkers/blood , Severity of Illness Index , Case-Control Studies , Interleukin-6/blood , Adult
6.
Biotechnol J ; 19(7): e2300577, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38987216

ABSTRACT

Microbial strain improvement through adaptive laboratory evolution (ALE) has been a key strategy in biotechnology for enhancing desired phenotypic traits. In this Biotech Method paper, we present an accelerated ALE (aALE) workflow and its successful implementation in evolving Cupriavidus necator H16 for enhanced tolerance toward elevated glycerol concentrations. The method involves the deliberate induction of genetic diversity through controlled exposure to divalent metal cations, enabling the rapid identification of improved variants. Through this approach, we observed the emergence of robust variants capable of growing in high glycerol concentration environments, demonstrating the efficacy of our aALE workflow. When cultivated in 10% v/v glycerol, the adapted variant Mn-C2-B11, selected through aALE, achieved a final OD600 value of 56.0 and a dry cell weight of 15.2 g L-1, compared to the wild type (WT) strain's final OD600 of 39.1 and dry cell weight of 8.4 g L-1. At an even higher glycerol concentration of 15% v/v, Mn-C2-B11 reached a final OD600 of 48.9 and a dry cell weight of 12.7 g L-1, in contrast to the WT strain's final OD600 of 9.0 and dry cell weight of 3.1 g L-1. Higher glycerol consumption by Mn-C2-B11 was also confirmed by high-performance liquid chromatography (HPLC) analysis. This adapted variant consumed 34.5 times more glycerol compared to the WT strain at 10% v/v glycerol. Our method offers several advantages over other reported ALE approaches, including its independence from genetically modified strains, specialized genetic tools, and potentially carcinogenic DNA-modifying agents. By utilizing divalent metal cations as mutagens, we offer a safer, more efficient, and cost-effective alternative for expansion of genetic diversity. With its ability to foster rapid microbial evolution, aALE serves as a valuable addition to the ALE toolbox, holding significant promise for the advancement of microbial strain engineering and bioprocess optimization.


Subject(s)
Cupriavidus necator , Glycerol , Cupriavidus necator/genetics , Cupriavidus necator/metabolism , Glycerol/metabolism , Glycerol/chemistry , Cations, Divalent , Directed Molecular Evolution/methods
7.
Rev Paul Pediatr ; 43: e2023203, 2024.
Article in English | MEDLINE | ID: mdl-38985050

ABSTRACT

OBJECTIVE: To evaluate the seasonality of acute bronchiolitis in Brazil during the 2020-2022 season and compare it with the previous seasons. METHODS: Data from the incidence of hospitalizations due to acute bronchiolitis in infants <1 year of age were obtained from the Department of Informatics of the Brazilian Public Health database for the period between 2016 and 2022. These data were also analyzed by macro-regions of Brazil (North, Northeast, Southeast, South, and Midwest). To describe seasonal and trend characteristics over time, we used the Seasonal Autoregressive Integrated Moving Averages Model. RESULTS: Compared to the pre-COVID-19 period, the incidence of hospitalizations related to acute bronchiolitis decreased by 97% during non-pharmacological interventions (March 2020 - August 2021) but increased by 95% after non-pharmacological interventions relaxation (September 2021 - December 2022), resulting in a 16% overall increase. During the pre-COVID-19 period, hospitalizations for acute bronchiolitis followed a seasonal pattern, which was disrupted in 2020-2021 but recovered in 2022, with a peak occurring in May, approximately 4% higher than the pre-COVID-19 peak. CONCLUSIONS: This study underscores the significant influence of COVID-19 interventions on acute bronchiolitis hospitalizations in Brazil. The restoration of a seasonal pattern in 2022 highlights the interplay between public health measures and respiratory illness dynamics in young children.


Subject(s)
Bronchiolitis , COVID-19 , Hospitalization , Interrupted Time Series Analysis , Seasons , Humans , Brazil/epidemiology , Infant , Bronchiolitis/epidemiology , Bronchiolitis/therapy , Incidence , Hospitalization/statistics & numerical data , Hospitalization/trends , COVID-19/epidemiology , Infant, Newborn , Acute Disease
8.
Reumatol Clin (Engl Ed) ; 20(6): 297-304, 2024.
Article in English | MEDLINE | ID: mdl-38991823

ABSTRACT

AIM: To describe the impact of the COVID-19 on the psychosocial health of patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and systemic lupus erythematosus (SLE). DESIGN: Longitudinal observational study of a series of patients with rheumatic disease. METHODS: The main outcome measure was impairment of the ability to participate in social activities, as measured using the PROMIS-APS instrument Short Form-8a. We evaluated social activities in various settings and performed a multivariate analysis to study the association between worsening of social participation during the COVID-19 pandemic and implicated factors. RESULTS: One hundred and twenty-five patients had completed the prospective follow-up: 40 with AR (32%), 42 with SpA (33.6%), and 43 with SLE (34.4%). Overall, poorer mean PROMIS scores were recorded after the COVID-19 pandemic for: satisfaction with social roles (p=0.029), depression (p=0.039), and ability to participate in social activities (p=0.024). The factors associated with ability to participate in social activities after the COVID-19 pandemic were older age (ß=-0.215; p=0.012), diagnosis of SLE (ß=-0.203; p=0.015), depression (ß=-0.295; p=0.003) and satisfaction with social roles (ß=0.211; p=0.037). CONCLUSION: The ability to participate in social activities after the COVID-19 pandemic is affected in patients with rheumatic disease, especially in SLE.


Subject(s)
COVID-19 , Rheumatic Diseases , Humans , COVID-19/psychology , COVID-19/epidemiology , Female , Male , Middle Aged , Longitudinal Studies , Adult , Rheumatic Diseases/psychology , Arthritis, Rheumatoid/psychology , Lupus Erythematosus, Systemic/psychology , Aged , Social Participation , Prospective Studies , Spondylarthritis/psychology , Depression/epidemiology , Depression/etiology , Pandemics
9.
Front Microbiol ; 15: 1416628, 2024.
Article in English | MEDLINE | ID: mdl-38989015

ABSTRACT

Background: Multidrug-resistant bacteria and the shortage of new antibiotics constitute a serious health problem. This problem has led to increased interest in the use of bacteriophages, which have great potential as antimicrobial agents but also carry the risk of inducing resistance. The objective of the present study was to minimize the development of phage resistance in Klebsiella pneumoniae strains by inhibiting quorum sensing (QS) and thus demonstrate the role of QS in regulating defense mechanisms. Results: Cinnamaldehyde (CAD) was added to K. pneumoniae cultures to inhibit QS and thus demonstrate the role of the signaling system in regulating the anti-phage defense mechanism. The QS inhibitory activity of CAD in K. pneumoniae was confirmed by a reduction in the quantitative expression of the lsrB gene (AI-2 pathway) and by proteomic analysis. The infection assays showed that the phage was able to infect a previously resistant K. pneumoniae strain in the cultures to which CAD was added. The results were confirmed using proteomic analysis. Thus, anti-phage defense-related proteins from different systems, such as cyclic oligonucleotide-based bacterial anti-phage signaling systems (CBASS), restriction-modification (R-M) systems, clustered regularly interspaced short palindromic repeat-Cas (CRISPR-Cas) system, and bacteriophage control infection (BCI), were present in the cultures with phage but not in the cultures with phage and CAD. When the QS and anti-phage defense systems were inhibited by the combined treatment, proteins related to phage infection and proliferation, such as the tail fiber protein, the cell division protein DamX, and the outer membrane channel protein TolC, were detected. Conclusion: Inhibition of QS reduces phage resistance in K. pneumoniae, resulting in the infection of a previously resistant strain by phage, with a significant increase in phage proliferation and a significant reduction in bacterial growth. QS inhibitors could be considered for therapeutic application by including them in phage cocktails or in phage-antibiotic combinations to enhance synergistic effects and reduce the emergence of antimicrobial resistance.

10.
J Med Virol ; 96(7): e29752, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38949191

ABSTRACT

Antiviral signaling, immune response and cell metabolism are dysregulated by SARS-CoV-2, the causative agent of COVID-19. Here, we show that SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10 induce a significant mitochondrial and metabolic reprogramming in A549 lung epithelial cells. While ORF9b, ORF9c and ORF10 induced largely overlapping transcriptomes, ORF3a induced a distinct transcriptome, including the downregulation of numerous genes with critical roles in mitochondrial function and morphology. On the other hand, all four ORFs altered mitochondrial dynamics and function, but only ORF3a and ORF9c induced a marked alteration in mitochondrial cristae structure. Genome-Scale Metabolic Models identified both metabolic flux reprogramming features both shared across all accessory proteins and specific for each accessory protein. Notably, a downregulated amino acid metabolism was observed in ORF9b, ORF9c and ORF10, while an upregulated lipid metabolism was distinctly induced by ORF3a. These findings reveal metabolic dependencies and vulnerabilities prompted by SARS-CoV-2 accessory proteins that may be exploited to identify new targets for intervention.


Subject(s)
COVID-19 , Mitochondria , SARS-CoV-2 , Viral Proteins , Humans , A549 Cells , COVID-19/metabolism , COVID-19/virology , COVID-19/pathology , Mitochondria/metabolism , Open Reading Frames , SARS-CoV-2/genetics , Transcriptome , Viral Proteins/genetics , Viral Proteins/metabolism , Viral Regulatory and Accessory Proteins/metabolism , Viral Regulatory and Accessory Proteins/genetics , Viroporin Proteins/metabolism
11.
Sci Rep ; 14(1): 15741, 2024 07 08.
Article in English | MEDLINE | ID: mdl-38977822

ABSTRACT

Rhythmic entrainment is a fundamental aspect of musical behavior, but the skills required to accurately synchronize movement to the beat seem to develop over many years. Motion capture studies of corporeal synchronization have shown immature abilities to lock in to the beat in children before age 5, and reliable synchronization ability in adults without musical training; yet there is a lack of data on full-body synchronization skills between early childhood and adulthood. To document typical rhythmic synchronization during middle childhood, we used a wireless motion capture device to measure period- and phase-locking of full body movement to rhythm and metronome stimuli in 6 to 11 year-old children in comparison with adult data. Results show a gradual improvement with age; however children's performance did not reach adult levels by age 12, suggesting that these skills continue to develop during adolescence. Our results suggest that in the absence of specific music training, full-body rhythmic entrainment skills improve gradually during middle childhood, and provide metrics for examining the continued maturation of these skills during adolescence.


Subject(s)
Music , Humans , Child , Male , Female , Child Development/physiology , Periodicity , Adult , Movement/physiology , Adolescent
12.
European J Pediatr Surg Rep ; 12(1): e50-e53, 2024 Jan.
Article in English | MEDLINE | ID: mdl-39071096

ABSTRACT

A 13-year-old male patient with marfanoid features and pectus excavatum with Haller index 4 and correction index of 38% underwent the Nuss procedure with cryoanalgesia 9 days prior, which transpired uneventfully. Preoperative spirometry was normal, and echocardiogram showed light aortic valve dilation. A month later, during a routine outpatient checkup, he referred middle abdominal pain, denying respiratory symptoms nor thoracic pain. He presented bilateral apical and right basal hypophonesis. Chest X-ray revealed bilateral pneumothorax and right pleural effusion. Consequently, the patient was admitted to the emergency room, and a chest computed tomography was ordered, reporting right apical blebs. Bilateral thoracoscopy was performed, and apexes were checked for pulmonary blebs to rule out primary pneumothorax. In the right chest, a wedge resection of a distorted area on the apex and pleuroabrasion were done. Four air leaking eschars were found when performing lung expansion under water as leaking test, corresponding to cryoanalgesia intercostal eschars, and subsequently closed by primary suture. In the left chest, there were no blebs. However, another four pleural lesions with intact pleura in the left lower lobe were also found. Postoperative course was uneventful and chest drains were removed 48 hours after surgery. He remains asymptomatic 21 months after discharge. Cryoanalgesia in pectus excavatum is spreading due to the improvement in postoperative pain control. However, some complications may occur.

13.
Proc Natl Acad Sci U S A ; 121(31): e2407546121, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39042682

ABSTRACT

Fragile X syndrome (FXS) is the most common genetic cause of autism spectrum disorder engendered by transcriptional silencing of the fragile X messenger ribonucleoprotein 1 (FMR1) gene. Given the early onset of behavioral and molecular changes, it is imperative to know the optimal timing for therapeutic intervention. Case reports documented benefits of metformin treatment in FXS children between 2 and 14 y old. In this study, we administered metformin from birth to Fmr1-/y mice which corrected up-regulated mitogen-2 activated protein kinase/extracellular signal-regulated kinase and mammalian/mechanistic target of rapamycin complex 1 signaling pathways and specific synaptic mRNA-binding targets of FMRP. Metformin rescued increased number of calls in ultrasonic vocalization and repetitive behavior in Fmr1-/y mice. Our findings demonstrate that in mice, early-in-life metformin intervention is effective in treating FXS pathophysiology.


Subject(s)
Fragile X Mental Retardation Protein , Fragile X Syndrome , Metformin , Metformin/pharmacology , Metformin/therapeutic use , Fragile X Syndrome/drug therapy , Fragile X Syndrome/genetics , Fragile X Syndrome/physiopathology , Fragile X Syndrome/metabolism , Animals , Fragile X Mental Retardation Protein/genetics , Fragile X Mental Retardation Protein/metabolism , Mice , Male , Mice, Knockout , Mechanistic Target of Rapamycin Complex 1/metabolism , Disease Models, Animal , Signal Transduction/drug effects
14.
Pediatr Transplant ; 28(5): e14810, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38894686

ABSTRACT

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy. In the last few years, after the publication of the consensus guidelines, with refined diagnostic criteria and improved awareness, FPIES is diagnosed with increased frequency. However, despite having a background of immune dysregulation, this complication has just been described once in the posttransplant setting, in an adult patient. To the best of our knowledge, there are no reports of pediatric patients developing FPIES after a hematopoietic stem cell transplant (HCT). METHODS: Retrospective review of a pediatric patient who developed severe FPIEs after a HCT. RESULTS: In this case report, the clinical presentation and diagnosis challenges of a pediatric patient who developed severe FPIES after HCT are described. The patient developed severe vomiting, diarrhea, lethargy, and shock and required admission to the pediatric intensive care unit in three occasions before the diagnosis was made. CONCLUSIONS: To the best of our knowledge, this is the first report of severe FPIES post-HCT in a pediatric patient. Physicians who are looking after pediatric patients in the post-HCT setting need to be aware of this possibility and include this entity in the differential diagnosis in order to reduce its associated morbidity.


Subject(s)
Enterocolitis , Food Hypersensitivity , Hematopoietic Stem Cell Transplantation , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Enterocolitis/etiology , Enterocolitis/diagnosis , Food Hypersensitivity/diagnosis , Food Hypersensitivity/etiology , Male , Dietary Proteins , Syndrome , Retrospective Studies , Female , Child, Preschool , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Postoperative Complications/therapy
15.
J Bras Pneumol ; 50(3): e20230292, 2024.
Article in English | MEDLINE | ID: mdl-38896732

ABSTRACT

OBJECTIVE: Cystic fibrosis (CF) affects multiple organs, the most severe consequences being observed in the lungs. Despite significant progress in developing CF transmembrane conductance regulator-specific treatments for CF lung disease, exploring alternative CF-targeted medications seems reasonable. We sought to evaluate the potential beneficial effects of oral benzbromarone as an adjuvant therapy in CF patients with reduced lung function. METHODS: This was a prospective open-label pilot study of oral benzbromarone (100 mg/day) administered once daily for 90 days. Patients were followed at a tertiary referral center in southern Brazil. Safety was assessed by the number of reported adverse events. Secondary objectives included percent predicted FEV1 (FEV1%) and pulmonary exacerbations. RESULTS: Ten patients were enrolled. Benzbromarone was found to be safe, with no serious drug-related adverse events. Eight patients completed the study; the median relative change in FEV1% tended to increase during the treatment, showing an 8% increase from baseline at the final visit. However, a nonparametric test showed that the change was not significant (p = 0.06). Of a total of ten patients, only one experienced at least one pulmonary exacerbation during the study. CONCLUSIONS: Oral benzbromarone appears to be safe, and improved FEV1% has been observed in patients with CF. Further assessment in larger trials is warranted to elucidate whether oral benzbromarone can be a potential adjuvant therapy for CF.


Subject(s)
Benzbromarone , Cystic Fibrosis , Humans , Cystic Fibrosis/drug therapy , Cystic Fibrosis/physiopathology , Pilot Projects , Male , Female , Benzbromarone/therapeutic use , Benzbromarone/administration & dosage , Prospective Studies , Adult , Treatment Outcome , Young Adult , Adolescent , Forced Expiratory Volume/drug effects , Uricosuric Agents/therapeutic use , Statistics, Nonparametric , Chemotherapy, Adjuvant , Time Factors
16.
Polymers (Basel) ; 16(11)2024 May 29.
Article in English | MEDLINE | ID: mdl-38891480

ABSTRACT

BACKGROUND: Sealing the peri-implant tissue is a determining factor for long-term implant survival. In the transmucosal region, the cervical fraction of the prosthetic crown is in contact with these tissues, so mucointegration will also be influenced by the biomaterial used for the prosthetic restoration. This study aims to compare the tissue response generated by definitive restorative materials and polymeric materials from a histological point of view. METHODS: This study performed an observational prospective cohort study in which biopsies of the peri-implant mucosa were taken after placement of implant-supported prosthetic restorations made of different materials (zirconium oxide, lithium disilicate, and PMMA). RESULTS: A statistically significant difference was observed in the increase in the thickness of the non-keratinized epithelium when comparing the definitive materials (zirconium oxide/lithium disilicate) vs. the provisional material (PMMA) and in the number of collagen fibers when comparing zirconium oxide and lithium disilicate. CONCLUSIONS: This study found that zirconia is the material that presents the most adequate biological response of peri-implant tissues. It shows a lower intensity of inflammatory cellular content, a total normality in the number of collagen fibers (the arrangement of the fibers is normal in 90% of the cases), and vascular proliferation of connective tissue in 83% of the cases. These parameters make it a material with a predictable response. Similarly, only the following slight statistically significant differences between the definitive and provisional materials are observed, indicating that the biological response generated by the provisional material (PMMA) is not very different from that obtained with the placement of the definitive restoration.

18.
Cancers (Basel) ; 16(12)2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38927913

ABSTRACT

This study aimed to analyze the effects of a team rowing-based training program on physical fitness and anthropometric parameters in female breast cancer survivors (n = 40; 56.78 ± 6.38 years). The participants were divided into two groups: one rowed in fixed-seat rowing (FSR) boats (n = 20; 56.35 ± 4.89 years), and the other rowed in sliding-seat rowing (SSR) boats (n = 20; 57.20 ± 7.7 years). Both groups engaged in two 75 min sessions per week for 24 weeks. Significant improvements were observed in both groups in terms of weight (FSR: -1.93 kg, SSR: -1.75 kg), body mass index (FSR: -0.73 kg/m2, SSR: -0.67 kg/m2), waist circumference (FSR: -2.83 cm, SSR: -3.66 cm), and hip circumference (FSR: -2.02 cm, SSR: -2.88 cm). Muscle strength improved in the lower extremities (jump test: FSR: 2.99 cm, SSR: 3.11 cm) and upper extremities (dominant: FSR: 4.13 kgf, SSR: 4.34 kgf; non-dominant: FSR: 3.67 kgf, SSR: 3.32 kgf). Aerobic capacity also improved, with the SSR group showing a greater increase (FSR: 63.05 m, SSR: 93.65 m). Flexibility tests revealed better results in the SSR group for both dominant (SSR: 1.75 cm vs. FSR: -5.55 cm) and non-dominant limbs (SSR: 1.72 cm vs. FSR: -3.81 cm). These findings suggest that the type of rowing modality can influence physical fitness outcomes, with the SSR group showing superior improvements compared to the FSR group.

19.
Nat Commun ; 15(1): 5359, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38918402

ABSTRACT

SDS22 forms an inactive complex with nascent protein phosphatase PP1 and Inhibitor-3. SDS22:PP1:Inhibitor-3 is a substrate for the ATPase p97/VCP, which liberates PP1 for binding to canonical regulatory subunits. The exact role of SDS22 in PP1-holoenzyme assembly remains elusive. Here, we show that SDS22 stabilizes nascent PP1. In the absence of SDS22, PP1 is gradually lost, resulting in substrate hyperphosphorylation and a proliferation arrest. Similarly, we identify a female individual with a severe neurodevelopmental disorder bearing an unstable SDS22 mutant, associated with decreased PP1 levels. We furthermore find that SDS22 directly binds to Inhibitor-3 and that this is essential for the stable assembly of SDS22:PP1: Inhibitor-3, the recruitment of p97/VCP, and the extraction of SDS22 during holoenzyme assembly. SDS22 with a disabled Inhibitor-3 binding site co-transfers with PP1 to canonical regulatory subunits, thereby forming non-functional holoenzymes. Our data show that SDS22, through simultaneous interaction with PP1 and Inhibitor-3, integrates the major steps of PP1 holoenzyme assembly.


Subject(s)
Protein Phosphatase 1 , Female , Humans , HEK293 Cells , Holoenzymes/metabolism , Phosphorylation , Protein Binding , Protein Phosphatase 1/metabolism , Protein Phosphatase 1/genetics , Valosin Containing Protein/metabolism , Valosin Containing Protein/genetics
SELECTION OF CITATIONS
SEARCH DETAIL