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1.
bioRxiv ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38617348

RESUMO

This study introduces the GeneTerrain Knowledge Map Representation (GTKM), a novel method for visualizing gene expression data in cancer research. GTKM leverages protein-protein interactions to graphically display differentially expressed genes (DEGs) on a 2-dimensional contour plot, offering a more nuanced understanding of gene interactions and expression patterns compared to traditional heatmap methods. The research demonstrates GTKM's utility through four case studies on glioblastoma (GBM) datasets, focusing on survival analysis, subtype identification, IDH1 mutation analysis, and drug sensitivities of different tumor cell lines. Additionally, a prototype website has been developed to showcase these findings, indicating the method's adaptability for various cancer types. The study reveals that GTKM effectively identifies gene patterns associated with different clinical outcomes in GBM, and its profiles enable the identification of sub-gene signature patterns crucial for predicting survival. The methodology promises significant advancements in precision medicine, providing a powerful tool for understanding complex gene interactions and identifying potential therapeutic targets in cancer treatment.

2.
Cureus ; 16(3): e55797, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38586618

RESUMO

The artery of Percheron (AOP) is a unique variant of the thalamic and midbrain perforating arteries. It originates from the P1 branch of the posterior cerebral artery (PCA) and supplies the bilateral paramedian thalami (BPT) along with variable contributions to the rostral midbrain. Four infarction patterns have been identified as a result of an AOP stroke, each associated with varying prognostic outcomes. We present an 89-year-old female with an AOP infarction and discuss the associated symptoms, implicated anatomy, and prognosis.

3.
RSC Adv ; 14(14): 9406-9439, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38516158

RESUMO

Supercapacitors are the latest development in the field of energy storage devices (ESDs). A lot of research has been done in the last few decades to increase the performance of supercapacitors. The electrodes of supercapacitors are modified by composite materials based on conducting polymers, metal oxide nanoparticles, metal-organic frameworks, covalent organic frameworks, MXenes, chalcogenides, carbon nanotubes (CNTs), etc. In comparison to rechargeable batteries, supercapacitors have advantages such as quick charging and high power density. This review is focused on the progress in the development of electrode materials for supercapacitors using composite materials based on conducting polymers, graphene, metal oxide nanoparticles/nanofibres, and CNTs. Moreover, we investigated different types of ESDs as well as their electrochemical energy storage mechanisms and kinetic aspects. We have also discussed the classification of different types of SCs; advantages and drawbacks of SCs and other ESDs; and the use of nanofibres, carbon, CNTs, graphene, metal oxide-nanofibres, and conducting polymers as electrode materials for SCs. Furthermore, modifications in the development of different types of SCs such as pseudo-capacitors, hybrid capacitors, and electrical double-layer capacitors are discussed in detail; both electrolyte-based and electrolyte-free supercapacitors are taken into consideration. This review will help in designing and fabricating high-performance supercapacitors with high energy density and power output, which will act as an alternative to Li-ion batteries in the future.

4.
Cureus ; 16(2): e54466, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38510880

RESUMO

INTRODUCTION: The pterion and asterion serve as crucial landmarks on the skull, representing the antero-lateral and postero-lateral fontanelles in neonates, respectively. In clinical practice, these points play a pivotal role in guiding the understanding of deeper structures and their relationships to the head's surface. The thin calvarium at these junctures is susceptible to fractures, and the underlying vessels are prone to tear, often leading to extradural hematoma formation, necessitating burr hole surgery for evacuation. MATERIAL AND METHODS: The study involved 40 human dry skulls in Indians (n= 27 male (10.8%), n= 13 female (5.2%)) of unknown age, evaluating morphometric characteristics of 80 pterions and asterions. Measurements were conducted using a digital caliper (SKADIOO±0.2mm/0.01") in millimeters on both sides of each skull. The investigation also included an examination of sutural patterns in Pterion and asterion. RESULTS: Three types of sutural patterns were identified in the pterion, the most common being the sphenoparietal variety (75% on the right, 70% on the left), followed by the epipteric variety, which was the second most common (11.3% on the right, 12.5% on the left), and then the frontotemporal type (1.3% on the right, 2.5% on the left). Two sutural patterns were observed in the asterion: type 1 (presence of sutural bone) in 17.9% of skulls and type 2 (absence of sutural bone) in 82.1%. CONCLUSION: The differences in pterion and asterion positions across various populations explored in previous studies motivated us to conduct this research in the Indian population. Our findings revealed that among Indians, the predominant pterion type is predominantly sphenoparietal, whereas type 2 is the most prevalent in asterion. Understanding the clinical significance of the pterion and asterion is crucial for healthcare professionals to ensure precise and safe surgical procedures, particularly for the effective treatment of head trauma patients.

5.
Indian J Surg Oncol ; 15(1): 136-144, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38511046

RESUMO

Calcifying aponeurotic fibroma (CAF) is a rare soft tissue tumor which falls under the WHO category of benign fibroblastic and myofibroblastic tumors. It typically occurs on the distal extremities (hands and foot) of children and adolescents. Other less common sites include wrists, ankles, trunk and rarely legs and arms. These tumors present as a painless soft tissue mass, arising in the subcutis, and are usually connected to tendons or aponeuroses. Computed tomography (CT) and magnetic resonance imaging (MRI) are the radiological investigations of choice; however, histopathology remains the diagnostic modality of choice for the diagnosis of CAF. We present a rare case of a 17-year-old boy who presented with a gradually progressive mass lesion on the leg which was later diagnosed as calcifying aponeurotic fibroma on histopathology.

6.
iScience ; 27(3): 109127, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38455979

RESUMO

NLP is a well-established field in ML for developing language models that capture the sequence of words in a sentence. Similarly, drug molecule structures can also be represented as sequences using the SMILES notation. However, unlike natural language texts, special characters in drug SMILES have specific meanings and cannot be ignored. We introduce a novel NLP-based method that extracts interpretable sequences and essential features from drug SMILES notation using N-grams. Our method compares these features to Morgan fingerprint bit-vectors using UMAP-based embedding, and we validate its effectiveness through two personalized drug screening (PSD) case studies. Our NLP-based features are sparse and, when combined with gene expressions and disease phenotype features, produce better ML models for PSD. This approach provides a new way to analyze drug molecule structures represented as SMILES notation, which can help accelerate drug discovery efforts. We have also made our method accessible through a Python library.

7.
Front Immunol ; 15: 1355012, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38482001

RESUMO

Macrophages play a central role in initiating, maintaining, and terminating inflammation. For that, macrophages respond to various external stimuli in changing environments through signaling pathways that are tightly regulated and interconnected. This process involves, among others, autoregulatory loops that activate and deactivate macrophages through various cytokines, stimulants, and other chemical mediators. Adaptor proteins play an indispensable role in facilitating various inflammatory signals. These proteins are dynamic and flexible modulators of immune cell signaling and act as molecular bridges between cell surface receptors and intracellular effector molecules. They are involved in regulating physiological inflammation and also contribute significantly to the development of chronic inflammatory processes. This is at least partly due to their involvement in the activation and deactivation of macrophages, leading to changes in the macrophages' activation/phenotype. This review provides a comprehensive overview of the 20 adaptor molecules and proteins that act as negative regulators of inflammation in macrophages and effectively suppress inflammatory signaling pathways. We emphasize the functional role of adaptors in signal transduction in macrophages and their influence on the phenotypic transition of macrophages from pro-inflammatory M1-like states to anti-inflammatory M2-like phenotypes. This endeavor mainly aims at highlighting and orchestrating the intricate dynamics of adaptor molecules by elucidating the associated key roles along with respective domains and opening avenues for therapeutic and investigative purposes in clinical practice.


Assuntos
Citocinas , Macrófagos , Humanos , Citocinas/metabolismo , Transdução de Sinais , Inflamação , Proteínas Adaptadoras de Transdução de Sinal/metabolismo
8.
Life Sci ; 345: 122584, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38527668

RESUMO

AIM: Sepsis is a life-threatening clinical syndrome comprising multiorgan dysfunctions caused by a disproportionate body immune response. There are several animal sepsis models which are based on cecum ligation, cecal puncture, and cecum slurry injection. The major limitation of all current sepsis models is the high variability owing to the variable degree of ligation, puncture and inconsistent microbial composition used for sepsis initiation. The primary objective of this work is to demonstrate the feasibility of a standardized method for sepsis development. MATERIALS AND METHODS: The cecal slurry bacterial culture was developed and preserved in glycerol stocks. Antibiotics aztreonam and vancomycin were used for generating several defined, enriched cecal slurry bacterial cultures. Mice survival was assessed until 48 hrs post injection, and the tissue samples were collected after 10 hrs from sepsis initiation. KEY FINDINGS: The results indicate that increasing polymicrobial load resulted in lower survival rates and was associated with the higher number of infiltrating immune cells and necrosis. H&E (haematoxylin & eosin) staining & serum markers revealed that septic mice exhibited increased inflammation and significant damage to the liver and kidneys. The defined Gram-negative and Gram-positive specific cecal slurry bacterial cultures were developed and their efficiency in inducing sepsis was characterized. SIGNIFICANCE: Enriched cecal slurry bacterial cultures can be stored in glycerol stocks at -80 °C. This has an ethical advantage of avoiding unnecessary animal euthanasia for each experiment and provides a standardization capability of sepsis development.


Assuntos
Glicerol , Sepse , Camundongos , Animais , Injeções Intraperitoneais , Sepse/tratamento farmacológico , Inflamação/complicações , Modelos Animais de Doenças , Ceco , Ligadura/efeitos adversos
9.
Int J Biol Macromol ; 264(Pt 1): 130614, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38447849

RESUMO

Mycobacterium tuberculosis (Mtb) caseinolytic protease B (ClpB) is a chaperone possessing a unique ability to resolubilize the aggregated proteins in vivo. ClpB has been shown to be important for the survival of Mtb within the host. Thus, it appears to be a promising target to develop new therapeutic molecules against tuberculosis. In this study, we have screened FDA approved compounds in silico to identify inhibitors against Mtb ClpB. In our screen, several compounds interacted with ClpB. The top four compounds, namely framycetin, gentamicin, ribostamycin and tobramycin showing the highest binding energy were selected for further investigation. MD simulations and tryptophan-based quenching of ClpB-drug complexes established that the selected inhibitors stably interacted with the target protein. The inhibitor and protein complexes were found to be stabilized by hydrogen bonding, and hydrophobic interactions. Although, the compounds did not affect the ATPase activity of ClpB significantly, the protein resolubilization activity of ClpB was remarkably reduced in their presence. All four compounds potently inhibited the growth of Mtb H37Ra. The antimycobacterial activity of the compounds appears to be due the inhibition of functional ClpB oligomer formation, in turn affecting its chaperonic activity.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Humanos , Mycobacterium tuberculosis/metabolismo , Chaperonas Moleculares/metabolismo , Peptídeo Hidrolases
10.
Int J Biol Macromol ; 264(Pt 1): 130626, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38453123

RESUMO

Silver-Carrageenan (Ag/Carr) nanocomposite film for food packing application by the green method using Argemone albiflora leaf extract has been developed in this study. Different plant parts of Argemone albiflora (blue stem prickly poppy) are used all over the world for the treatment of microbial infections, jaundice, skin diseases etc. GC-MS analysis was used to examine the phytochemical found in the Argemone albiflora leaf extract which reduces the metal ions to nanoscale. The biopolymer employed in the synthesis of nanocomposite film was carrageenan, a natural carbohydrate (polysaccharide) extracted from edible red seaweeds. We developed a food packing that is biodegradable, eco-friendly, economical and free from harmful chemicals. These films possess better UV barrier and mechanical and antimicrobial properties with 1 mM AgNO3 solution. The presence of silver nanoparticles in the carrageenan matrix was evident from FESEM. The mechanical properties were analysed by a Universal testing machine (UTM) and different properties like water vapour permeability (WVP), moisture content (MC) and total soluble matter (TSM) important for food packing applications were also analysed. The antimicrobial properties of the synthesized film samples were studied against E. coli and S. aureus pathogenic bacteria. These films were employed for the storage of cottage cheese (dairy product) and strawberries (fruit). This packing increased the shelf life of the packed food effectively. Ag/Carr films are biodegradable within four weeks.


Assuntos
Anti-Infecciosos , Argemone , Nanopartículas Metálicas , Nanocompostos , Carragenina/química , Prata/química , Embalagem de Alimentos , Nanopartículas Metálicas/química , Escherichia coli , Staphylococcus aureus , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Nanocompostos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Antibacterianos/farmacologia , Antibacterianos/química
11.
Artigo em Inglês | MEDLINE | ID: mdl-38454308

RESUMO

BACKGROUND: Injured patients are at an increased risk of developing deep vein thrombosis (DVT) and pulmonary embolism (PE). Inferior vena cava (IVC) filters have been used in injured patients to prevent venous thromboembolism (VTE), but current evidence-based guidelines are lacking. METHODS: Questions regarding IVC filter use in injured patients with clearly defined Population(s), Intervention(s), Comparison(s), and appropriately selected Outcomes (PICO) were formulated. The study sought to understand the evidence behind use of ultra short term IVC filters and use of IVC filters in injured patients with and without known VTE who are unable to receive therapeutic anticoagulation and chemoprophylaxis, respectively. A literature search and review was conducted, followed by meta-analysis. The quality of evidence was assessed per Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. RESULTS: There were twenty-one studies that were analyzed. Three studies were randomized controlled trials (RCTs), three were observational studies, and fifteen studies were retrospective studies. In injured patients without known acute VTE who cannot receive chemoprophylaxis, we recommend against placement of an IVC filter due to associated higher rate of mortality, DVT, PE, and length of stay. The quality of evidence was assessed to be low. In injured patients with known DVT who cannot receive chemoprophylaxis we conditionally recommend against placement of an IVC filter. The quality of evidence was assessed to be very low. No recommendations can be made with respect to placement of ultra short term IVC filters based upon available data. CONCLUSION: IVC filters should not be placed routinely for prophylaxis in injured adult patients without known VTE who cannot receive chemoprophylaxis. The taskforce conditionally recommends against the placement of IVC filter in injured adult patients with known DVT who cannot receive chemoprophylaxis. LEVEL OF EVIDENCE: Guideline; Systematic review/meta-analysis, level IV.

12.
Sci Rep ; 14(1): 3542, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38346989

RESUMO

This article reports the development of a microscopy imaging system that gives feasibility for studying spatio-temporal dynamics of physiological activities of alive biological specimens (over entire volume not only for a particular section, i.e., in 4D). The imaging technology facilitates to obtain two image frames of a section of the larger specimen ([Formula: see text]) with different FOVs at different resolutions or magnifications simultaneously in real-time (in addition to recovery of 3D (volume) information). Again, this imaging system addresses the longstanding challenges of housing multiple light sources (6 at the maximum till date) in microscopy (in general) and light sheet fluorescence microscopy (LSFM) (in particular), by using a tuneable pulsed laser source (with an operating wavelength in the range [Formula: see text]-670 nm) in contrast to the conventional CW laser source being adopted for inducing photo-excitation of tagged fluorophores. In the present study, we employ four wavelengths ([Formula: see text] 488 nm, 585 nm, 590 nm, and 594 nm). Our study also demonstrates quantitative characterization of spatio-temporal dynamics (velocity-both amplitude and direction) of organelles (mitochondria) and their mutual correlationships. Mitochondria close to the nucleus (or in clustered cells) are observed to possess a lower degree of freedom in comparison to that at the cellular periphery (or isolated cells). In addition, the study demonstrates real-time observation and recording of the development and growth of all tracheal branches during the entire period ([Formula: see text] min) of embryonic development (Drosophila). The experimental results-with experiments being conducted in various and diversified biological specimens (Drosophila melanogaster, mouse embryo, and HeLa cells)-demonstrate that the study is of great scientific impact both from the aspects of technology and biological sciences.


Assuntos
Drosophila melanogaster , Drosophila , Humanos , Animais , Camundongos , Células HeLa , Estudos de Tempo e Movimento , Microscopia de Fluorescência/métodos
13.
Environ Res ; 250: 118492, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38373550

RESUMO

Dioxin-like pollutants (DLPs), such as polychlorinated biphenyl 126 (PCB 126), are synthetic chemicals classified as persistent organic pollutants. They accumulate in adipose tissue and have been linked to cardiometabolic disorders, including fatty liver disease. The toxicity of these compounds is associated with activation of the aryl hydrocarbon receptor (Ahr), leading to the induction of phase I metabolizing enzyme cytochrome P4501a1 (Cyp1a1) and the subsequent production of reactive oxygen species (ROS). Recent research has shown that DLPs can also induce the xenobiotic detoxification enzyme flavin-containing monooxygenase 3 (FMO3), which plays a role in metabolic homeostasis. We hypothesized whether genetic deletion of Fmo3 could protect mice, particularly in the liver, where Fmo3 is most inducible, against PCB 126 toxicity. To test this hypothesis, male C57BL/6 wild-type (WT) mice and Fmo3 knockout (Fmo3 KO) mice were exposed to PCB 126 or vehicle (safflower oil) during a 12-week study, at weeks 2 and 4. Various analyses were performed, including hepatic histology, RNA-sequencing, and quantitation of PCB 126 and F2-isoprostane concentrations. The results showed that PCB 126 exposure caused macro and microvesicular fat deposition in WT mice, but this macrovesicular fatty change was absent in Fmo3 KO mice. Moreover, at the pathway level, the hepatic oxidative stress response was significantly different between the two genotypes, with the induction of specific genes observed only in WT mice. Notably, the most abundant F2-isoprostane, 8-iso-15-keto PGE2, increased in WT mice in response to PCB 126 exposure. The study's findings also demonstrated that hepatic tissue concentrations of PCB 126 were higher in WT mice compared to Fmo3 KO mice. In summary, the absence of FMO3 in mice led to a distinctive response to dioxin-like pollutant exposure in the liver, likely due to alterations in lipid metabolism and storage, underscoring the complex interplay of genetic factors in the response to environmental toxins.

14.
J Leukoc Biol ; 115(4): 738-749, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38207130

RESUMO

Generally, fasting and refeeding confer anti- and proinflammatory effects, respectively. In humans, these caloric-load interventions function, in part, via regulation of CD4+ T cell biology. However, mechanisms orchestrating this regulation remain incomplete. We employed integrative bioinformatics of RNA sequencing and high-performance liquid chromatography-mass spectrometry data to measure serum metabolites and gene expression of peripheral blood mononuclear cells isolated from fasting and refeeding in volunteers to identify nutrient-load metabolite-driven immunoregulation. Propionate, a short chain fatty acid (SCFA), and the SCFA-sensing G protein-coupled receptor 43 (ffar2) were coordinately and inversely regulated by fasting and refeeding. Propionate and free fatty acid receptor agonists decreased interferon-γ and interleukin-17 and significantly blunted histone deacetylase activity in CD4+ T cells. Furthermore, propionate blunted nuclear factor κB activity and diminished interleukin-6 release. In parallel, propionate reduced phosphorylation of canonical T helper 1 (TH1) and TH17 regulators, STAT1 and STAT3, respectively. Conversely, knockdown of free fatty acid receptors significantly attenuated the anti-inflammatory role of propionate. Interestingly, propionate recapitulated the blunting of CD4+ TH cell activation in primary cells from obese individuals, extending the role of this metabolite to a disease associated with low-grade inflammation. Together, these data identify a nutrient-load responsive SCFA-G protein-coupled receptor linked pathway to regulate CD4+ TH cell immune responsiveness.


Assuntos
Ácidos Graxos não Esterificados , Propionatos , Humanos , Propionatos/farmacologia , Leucócitos Mononucleares , Receptores Acoplados a Proteínas G/genética , Obesidade
15.
J Am Med Inform Assoc ; 31(4): 875-883, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38269583

RESUMO

OBJECTIVE: Evaluate the impact of community tele-paramedicine (CTP) on patient experience and satisfaction relative to community-level indicators of health disparity. MATERIALS AND METHODS: This mixed-methods study evaluates patient-reported satisfaction and experience with CTP, a facilitated telehealth program combining in-home paramedic visits with video visits by emergency physicians. Anonymous post-CTP visit survey responses and themes derived from directed content analysis of in-depth interviews from participants of a randomized clinical trial of mobile integrated health and telehealth were stratified into high, moderate, and low health disparity Community Health Districts (CHD) according to the 2018 New York City (NYC) Community Health Survey. RESULTS: Among 232 CTP patients, 55% resided in high or moderate disparity CHDs but accounted for 66% of visits between April 2019 and October 2021. CHDs with the highest proportion of CTP visits were more adversely impacted by social determinants of health relative to the NYC average. Satisfaction surveys were completed in 37% of 2078 CTP visits between February 2021 and March 2023 demonstrating high patient satisfaction that did not vary by community-level health disparity. Qualitative interviews conducted with 19 patients identified differing perspectives on the value of CTP: patients in high-disparity CHDs expressed themes aligned with improved health literacy, self-efficacy, and a more engaged health system, whereas those from low-disparity CHDs focused on convenience and uniquely identified redundancies in at-home services. CONCLUSIONS: This mixed-methods analysis suggests CTP bridges the digital health divide by facilitating telehealth in communities negatively impacted by health disparities.


Assuntos
60713 , Telemedicina , Humanos , Iniquidades em Saúde , Avaliação de Resultados da Assistência ao Paciente , Satisfação do Paciente
16.
Am J Med ; 137(4): 321-330.e7, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38190959

RESUMO

PURPOSE: There are concerns that transcatheter or surgical aortic valve replacement (TAVR/SAVR) procedures are preferentially available to White patients. Our objective was to examine differences in utilization of aortic valve replacement and outcomes by race/ethnicity in the US for patients with aortic stenosis. METHODS: We performed a serial cross-sectional cohort study of 299,976 Medicare beneficiaries hospitalized with principal diagnosis of aortic stenosis between 2012 and 2019 stratified by self-reported race/ethnicity (Black, Hispanic, Asian, Native American, and White). Outcomes included aortic valve replacement rates within 6 months of index hospitalization and associated procedural outcomes, including 30-day readmission, 30-day and 1-year mortality. RESULTS: Within 6 months of an index admission for aortic stenosis, 86.8% (122,457 SAVR; 138,026 TAVR) patients underwent aortic valve replacement. Overall, compared with White people, Black (HR 0.87 [0.85-0.89]), Hispanic (0.92 [0.88-0.96]), and Asian (0.95 [0.91-0.99]) people were less likely to receive aortic valve replacement. Among patients who were admitted emergently/urgently, White patients (41.1%, 95% CI, 40.7-41.4) had a significantly higher aortic valve replacement rate compared with Black (29.6%, 95% CI, 28.3-30.9), Hispanic (36.6%, 95% CI, 34.0-39.3), and Asian patients (35.4%, 95% CI, 32.3-38.9). Aortic valve replacement rates increased annually for all race/ethnicities. There were no significant differences in 30-day or 1-year mortality by race/ethnicity. CONCLUSIONS: Aortic valve replacement rates within 6 months of aortic stenosis admission are lower for Black, Hispanic, and Asian people compared to White people. These race-related differences in aortic stenosis treatment reflect complex issues in diagnosis and management, warranting a comprehensive reassessment of the entire care spectrum for disadvantaged populations.


Assuntos
Estenose da Valva Aórtica , Implante de Prótese de Valva Cardíaca , Substituição da Valva Aórtica Transcateter , Humanos , Idoso , Estados Unidos/epidemiologia , Valva Aórtica/cirurgia , Estudos Transversais , Medicare , Resultado do Tratamento , Estenose da Valva Aórtica/cirurgia , Fatores de Risco
17.
Sci Signal ; 17(821): eadg2622, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38289985

RESUMO

Targeted degradation regulates the activity of the transcriptional repressor Bcl6 and its ability to suppress oxidative stress and inflammation. Here, we report that abundance of endothelial Bcl6 is determined by its interaction with Golgi-localized pannexin 3 (Panx3) and that Bcl6 transcriptional activity protects against vascular oxidative stress. Consistent with data from obese, hypertensive humans, mice with an endothelial cell-specific deficiency in Panx3 had spontaneous systemic hypertension without obvious changes in channel function, as assessed by Ca2+ handling, ATP amounts, or Golgi luminal pH. Panx3 bound to Bcl6, and its absence reduced Bcl6 protein abundance, suggesting that the interaction with Panx3 stabilized Bcl6 by preventing its degradation. Panx3 deficiency was associated with increased expression of the gene encoding the H2O2-producing enzyme Nox4, which is normally repressed by Bcl6, resulting in H2O2-induced oxidative damage in the vasculature. Catalase rescued impaired vasodilation in mice lacking endothelial Panx3. Administration of a newly developed peptide to inhibit the Panx3-Bcl6 interaction recapitulated the increase in Nox4 expression and in blood pressure seen in mice with endothelial Panx3 deficiency. Panx3-Bcl6-Nox4 dysregulation occurred in obesity-related hypertension, but not when hypertension was induced in the absence of obesity. Our findings provide insight into a channel-independent role of Panx3 wherein its interaction with Bcl6 determines vascular oxidative state, particularly under the adverse conditions of obesity.


Assuntos
Hipertensão , Fatores de Transcrição , Animais , Humanos , Camundongos , Diferenciação Celular , Proliferação de Células/fisiologia , Conexinas/metabolismo , Peróxido de Hidrogênio/farmacologia , Obesidade , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Fatores de Transcrição/metabolismo
18.
J Pediatr Ophthalmol Strabismus ; : 1-8, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38275203

RESUMO

PURPOSE: To assess patient satisfaction within pediatric ophthalmology and identify trends in patient sentiment. METHODS: Pediatric ophthalmologists in the United States were identified using the American Association for Pediatric Ophthalmology and Strabismus member directory. Demographic data were recorded using publicly available websites. Online written reviews and Stars ratings were obtained from Healthgrades.com. A sentiment analysis package, Valence Aware Dictionary for Sentimental Reasoning (VADER), was used to generate a compound score of reviews, and word frequency analyses were applied. RESULTS: A total of 377 pediatric ophthalmologists (2,640 online reviews) were evaluated. Physicians received an average of 4.22/5 Stars and a compound sentiment score of 0.56, indicating positive sentiment. No differences in scores were observed by gender or location, although physicians with fewer years in practice had higher Stars ratings compared to peers (P < .001). The three most common words in the word frequency analysis of all reviews were "surgery," "staff," and "time," with heavy emphasis on bedside manner and addressing patient concerns. CONCLUSIONS: This study demonstrates overall high patient satisfaction in pediatric ophthalmology care, with differences in sentiment based on physician demographic features. The study highlights that patient perspective is influenced by non-clinical features of care. These data may be used by pediatric ophthalmologists seeking to improve health care delivery.[J Pediatr Ophthalmol Strabismus. 20XX;X(X):XXX-XXX.].

19.
Struct Heart ; 8(1): 100234, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38283574

RESUMO

In 2022, the Food and Drug Administration approved a second mitral transcatheter edge-to-edge repair device for the treatment of primary mitral regurgitation (PASCAL Precision Transcatheter Valve Repair System, Edwards Lifesciences, Irvine, CA). The PASCAL Precision system consists of a guide sheath, implant system, and accessories. The implant system consists of a steerable catheter, an implant catheter, and the implant (PASCAL or PASCAL Ace). The guide sheath and steerable catheter move and flex independently from each other and are not keyed, allowing for freedom of rotation in three dimensions. This manuscript provides an overview of the PASCAL Precision system and describes the basic and advanced steering maneuvers to facilitate effective and safe mitral transcatheter edge-to-edge repair.

20.
BMC Public Health ; 24(1): 299, 2024 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-38273246

RESUMO

BACKGROUND: Patients with TB have additional nutritional requirements and thus additional costs to the household. Ni-kshay Poshan Yojana(NPY) is a Direct Benefit Transfer (DBT) scheme under the National Tuberculosis Elimination Programme(NTEP) in India which offers INR 500 monthly to all notified patients with TB for nutritional support during the period of anti-TB treatment. Five years after its implementation, we conducted the first nationwide evaluation of NPY. METHODS: In our retrospective cohort study using programmatic data of patients notified with TB in nine randomly selected Indian states between 2018 and 2022, we estimated the proportion of patients who received at least one NPY instalment and the median time to receive the first instalment. We determined the factors associated (i) with non-receipt of NPY using a generalised linear model with Poisson family and log link and (ii) with time taken to receive first NPY benefit in 2022 using quantile regression at 50th percentile. RESULTS: Overall, 3,712,551 patients were notified between 2018 and 2022. During this period, the proportion who received at least one NPY instalment had increased from 56.9% to 76.1%. Non-receipt was significantly higher among patients notified by private sector (aRR 2.10;2.08,2.12), reactive for HIV (aRR 1.69;1.64,1.74) and with missing/undetermined diabetic status (aRR 2.02;1.98,2.05). The median(IQR) time to receive the first instalment had reduced from 200(109,331) days in 2018 to 91(51,149) days in 2022. Patients from private sector(106.9;106.3,107.4days), those with HIV-reactive (103.7;101.8,105.7days), DRTB(104.6;102.6,106.7days) and missing/undetermined diabetic status (115.3;114,116.6days) experienced longer delays. CONCLUSIONS: The coverage of NPY among patients with TB had increased and the time to receipt of benefit had halved in the past five years. Three-fourths of the patients received at least one NPY instalment, more than half of whom had waited over three months to receive the first instalment. NTEP has to focus on timely transfer of benefits to enable patients to meet their additional nutritional demands, experience treatment success and avoid catastrophic expenditure.


Assuntos
Diabetes Mellitus , Soropositividade para HIV , Humanos , Estudos Retrospectivos , Apoio Nutricional , Índia/epidemiologia
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