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1.
Vet Med Sci ; 10(4): e1521, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38952271

RESUMO

BACKGROUND: Cynomolgus monkeys (Macaca fascicularis) are essential in biomedical research, including reproductive studies. However, the application of human estimated foetal weight (EFW) formulas using ultrasonography (USG) in these non-human primates is not well established. OBJECTIVES: This study aims to evaluate the applicability of human EFW formulas for estimating foetal weight in cynomolgus monkeys at approximately 130 days of gestation. METHODS: Our study involved nine pregnant cynomolgus monkeys. We measured foetal parameters, including biparietal diameter, head circumference, abdominal circumference and femur length using USG. The EFW was calculated using 11 human EFW formulas. The actual birthweight (ABW) was recorded following Cesarean section, the day after the EFW calculation. For comparing EFW and ABW, we employed statistical methods such as mean absolute percentage error (APE) and Bland-Altman analysis. RESULTS: The ABW ranged between 200.36 and 291.33 g. Among the 11 formulas, the Combs formula showed the lowest APE (4.3%) and highest correlation with ABW (p < 0.001). Notably, EFW and ABW differences for the Combs formula were ≤5% in 66.7% and ≤10% in 100% of cases. The Bland-Altman analysis supported these results, showing that all cases fell within the limits of agreement. CONCLUSIONS: The Combs formula is applicable for estimating the weight of cynomolgus monkey fetuses with USG at approximately 130 days of gestation. Our observations suggest that the Combs formula can be applied in the prenatal care and biomedical research of this species.


Assuntos
Peso ao Nascer , Peso Fetal , Macaca fascicularis , Ultrassonografia Pré-Natal , Animais , Macaca fascicularis/embriologia , Macaca fascicularis/fisiologia , Feminino , Peso Fetal/fisiologia , Gravidez , Ultrassonografia Pré-Natal/veterinária , Humanos
2.
Phytochemistry ; 226: 114205, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38971497

RESUMO

From the Cynanchum wilfordii roots, 32 compounds, including 5 previously undescribed (1, 4-6, 12) and 27 known (2, 3, 7-11, 13-32) compounds, were isolated, and their structures were elucidated using NMR spectroscopic data and MS data aided by ECD calculations or the modified Mosher's reaction. All isolates were tested for their inhibitory effects on proprotein convertase subtilisin/kexin type 9 (PCSK9) secretion. Among the isolates, compound 4, a methyl cholesterol analog, exhibited the most potent effect in reducing PCSK9 secretion, along with PCSK9 downregulation at the mRNA and protein levels via FOXO1/3 upregulation. Moreover, compound 4 attenuated statin-induced PCSK9 expression and enhanced the uptake of DiI-LDL low-density lipoprotein. Thus, compound 4 is suggested to be a potential candidate for controlling cholesterol levels.

3.
APL Bioeng ; 8(3): 036103, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38983108

RESUMO

Duodenal mucosal resurfacing (DMR) by thermal ablation of the duodenal mucosa is a minimally invasive endoscopic procedure for controlling metabolic syndrome (MS). However, thermal energy can cause adverse effects due to deep mucosal injury, necessitating an additional mucosal lifting process, which complicate the procedures. Therefore, we aimed to develop a similar procedure using non-thermal photodynamic therapy (PDT) for DMR using a highly functional metal stent covered with photosensitizers (PSs) to minimize the potential risks of thermal ablation injury. We developed a novel PS stent enabling the controlled release of radical oxygen species with specific structures to prevent stent migration and duodenal stricture after ablation and performed an animal study (n = 8) to demonstrate the feasibility and safety of PDT for DMR. The stents were placed for 7 days to prevent duodenal strictures after PDT. To confirm PDT efficacy, we stained for gastric inhibitory polypeptide (GIP) and glucose transporter isoform 1. The PS stents were deployed, and PDT was applied without evidence of duodenal stricture, pancreatitis, or hemorrhage in any of the pigs. Microscopic evaluation indicated apoptosis of the mucosal cells in the irradiated duodenum on days 7 and 14, which recovered after day 28. Immunohistochemistry revealed suppressed GIP expression in the mucosal wall of the irradiated duodenum. Endoscopic PDT for DMR using PS stents could be applied safely in a porcine model and may result in decreased GIP secretion, which is a crucial mechanism in MS treatment. Further clinical studies are required to explore its safety and efficacy in patients with MS.

4.
Front Vet Sci ; 11: 1409386, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39027909

RESUMO

Sterilization and castration have been synonyms for thousands of years. Making an animal sterile meant to render them incapable of producing offspring. Castration or the physical removal of the testes was discovered to be the most simple but reliable method for managing reproduction and sexual behavior in the male. Today, there continues to be global utilization of castration in domestic animals. More than six hundred million pigs are castrated every year, and surgical removal of testes in dogs and cats is a routine practice in veterinary medicine. However, modern biological research has extended the meaning of sterilization to include methods that spare testis removal and involve a variety of options, from chemical castration and immunocastration to various methods of vasectomy. This review begins with the history of sterilization, showing a direct link between its practice in man and animals. Then, it traces the evolution of concepts for inducing sterility, where research has overlapped with basic studies of reproductive hormones and the discovery of testicular toxicants, some of which serve as sterilizing agents in rodent pests. Finally, the most recent efforts to use the immune system and gene editing to block hormonal stimulation of testis function are discussed. As we respond to the crisis of animal overpopulation and strive for better animal welfare, these novel methods provide optimism for replacing surgical castration in some species.

5.
Fish Shellfish Immunol ; 152: 109770, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39025166

RESUMO

Prohibitin 1 (PHB1) is ubiquitously expressed in multiple compartments within cells and is involved in the cell cycle, cell signaling, apoptosis, transcriptional regulation, and mitochondrial biogenesis at the cellular level and in the inflammation-associated and immunological functions of B and T lymphocytes. PHB1 is an important protein that performs antioxidant regulation and immune functions inside and outside cells but has not been sufficiently studied in teleost fish. Our study aimed to elucidate the functional properties and gain new insights into the biological processes and immune system of red seabream (Pagrus major), a commercially important fish cultured in South Korea and East Asia. PHB1 mRNA was most abundantly expressed in the head kidney of healthy red seabream, and significant changes in its expression were observed after artificial infection with bacteria and viruses. On analysis, reporter gene was also significantly upregulated by polyinosinic-polycytidylic acid, lipopolysaccharides, and hydrogen peroxide. Consequent to the functional characterization of PHB1 in cells via recombinant protein preparation, the activity of leukocytes was enhanced and the reactive oxygen species-induced stress in red blood cells was reduced. The results reveal the functional characteristics of PHB1 and provide new insights into the biological processes and immune system of P. major, with beneficial implications in the study of stress responses.

6.
Nanoscale ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39011622

RESUMO

Rapidly fabricating flexible and stretchable sensors on nonplanar surfaces is crucial for wearable device applications. We employed a novel fabrication method, incorporating molds and gels into electroless plating, to enable direct printing of sensors on a wide array of surfaces, from those with up to 100 µm profile heights to hydrogels with a Young's modulus of 100 kPa. This coatable strain (CS) sensor offers several potential advantages. Firstly, it is designed to circumvent the typical limitations of limited flexibility, plastic deformation, and low repeatability found in viscoelastic polymers by being directly coated onto the surface without requiring a substrate. Secondly, it potentially increases the effective contact area and signal-to-noise ratio by eliminating voids between the sensor and the surface. Finally, the CS sensor can obtain any desired patterning at room temperature in a matter of minutes, significantly reducing energy and time consumption. In this study, we demonstrated the versatility of the CS sensor by applying it to a range of substrates, showcasing its adaptability to diverse materials, surface roughness levels, and Young's modulus values. Our primary focus was on plant growth monitoring, a challenging application that showcased the sensor's efficacy on surfaces like needles, hairy leaves, and fruits. These applications, traditionally difficult for conventional polymer-based sensors, serve to illustrate the CS sensor's potential in a range of complex environmental contexts. The successful deployment of the CS sensor in these settings suggests its broader applicability in various scientific and technological fields, potentially contributing to significant developments in the area of wearable devices and beyond.

7.
Polymers (Basel) ; 16(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-39000693

RESUMO

The development of high-filled 3D printing resin necessitates a bonding protocol for dental indirect restorations to achieve optimal bond strength after cementation. This study evaluates shear bond strengths of high-filler 3D printed materials for permanent restorations with various surface treatments. Rodin Sculpture 1.0 (50% lithium disilicate fillers) and 2.0 Ceramic Nanohybrid (>60% zirconia and lithium disilicate fillers) were tested, with Aelite All-Purpose Body composite resin as control. Samples were prepared, post-cured, and sandblasted with alumina (25 µm). Surface roughness was analyzed using an optical profilometer. Two bonding protocols were compared. First, groups were treated with lithium disilicate silane (Porcelain Primer) or zirconia primer (Z-Prime Plus) or left untreated without a bonding agent. Beam-shaped resin cement (DuoLink Universal) specimens were bonded and stored in a 37 °C water bath. Second, additional sets of materials were coated with a bonding agent (All-Bond Universal), either followed by silane application or left untreated. These sets were then similarly stored alongside resin cement specimens. Shear bond tests were performed after 24 h. SEM images were taken after debonding. One-Way ANOVA and post hoc Duncan were performed for the statistical analysis. Rodin 1.0 exhibited increased adhesive failure with silane or zirconia primer coating, but significantly improved bond strengths with bonding agent application. Rodin 2.0 showed consistent bond strengths regardless of bonding agent application, but cohesive failure rates increased with bonding agent and filler coating. In all groups, except for Rodin 1.0 without bonding agent, silane coating increased cohesive failure rate. In conclusion, optimal shear bond strength for high-filler 3D printing materials can be achieved with silane coating and bonding agent application.

8.
Drugs Aging ; 41(7): 583-600, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38954400

RESUMO

The objective of this review is to summarize and appraise the research methodology, emerging findings, and future directions in pharmacoepidemiologic studies assessing the benefits and harms of pharmacotherapies in older adults with different levels of frailty. Older adults living with frailty are at elevated risk for poor health outcomes and adverse effects from pharmacotherapy. However, current evidence is limited due to the under-enrollment of frail older adults and the lack of validated frailty assessments in clinical trials. Recent advancements in measuring frailty in administrative claims and electronic health records (database-derived frailty scores) have enabled researchers to identify patients with frailty and to evaluate the heterogeneity of treatment effects by patients' frailty levels using routine health care data. When selecting a database-derived frailty score, researchers must consider the type of data (e.g., different coding systems), the length of the predictor assessment period, the extent of validation against clinically validated frailty measures, and the possibility of surveillance bias arising from unequal access to care. We reviewed 13 pharmacoepidemiologic studies published on PubMed from 2013 to 2023 that evaluated the benefits and harms of cardiovascular medications, diabetes medications, anti-neoplastic agents, antipsychotic medications, and vaccines by frailty levels. These studies suggest that, while greater frailty is positively associated with adverse treatment outcomes, older adults with frailty can still benefit from pharmacotherapy. Therefore, we recommend routine frailty subgroup analyses in pharmacoepidemiologic studies. Despite data and design limitations, the findings from such studies may be informative to tailor pharmacotherapy for older adults across the frailty spectrum.


Assuntos
Fragilidade , Farmacoepidemiologia , Humanos , Farmacoepidemiologia/métodos , Idoso , Idoso Fragilizado , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia
9.
J Am Geriatr Soc ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38979879

RESUMO

BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) introduced chronic care management (CCM) services in 2015 for patients with multiple chronic diseases. Few studies examine the utilization of CCM services by geographic region, sociodemographic, and clinical characteristics. METHODS: We used 2014-2019 Medicare claims data from a 5% random sample of fee-for-service beneficiaries aged 65 years or over. We included beneficiaries potentially eligible for CCM services because they had multiple chronic conditions (1,073,729 in 2015 and 1,130,523 in 2019). We calculated the proportion of potentially eligible beneficiaries receiving CCM service each year for the total population and by geographic region, sociodemographic, and clinical characteristics. RESULTS: The proportion of beneficiaries with two or more chronic conditions receiving CCM services increased from 1.1% in 2015 to 3.4% in 2019. The increase in CCM use was higher in the southern region, among dually eligible beneficiaries and beneficiaries with a greater burden of chronic conditions (2-5 conditions vs ≥10 conditions: 0.7% vs 2.0% in 2015; 2.1% vs 7.0% in 2019) and frailty (robust vs severely frail: 0.6% vs 3.3% in 2015; 1.9% vs 9.4% in 2019). Nearly one out of five recipients did not continue CCM service after the initial service. CONCLUSION: We found that CCM service is being used by a very small fraction of eligible patients. Barriers and facilitators to more effective CCM adoption should be identified and incorporated into strategies that encourage more widespread use of this Medicare benefit.

10.
Immune Netw ; 24(3): e19, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38974213

RESUMO

The influenza virus poses a global health burden. Currently, an annual vaccine is used to reduce influenza virus-associated morbidity and mortality. Most influenza vaccines have been developed to elicit neutralizing Abs against influenza virus. These Abs primarily target immunodominant epitopes derived from hemagglutinin (HA) or neuraminidase (NA) of the influenza virus incorporated in vaccines. However, HA and NA are highly variable proteins that are prone to antigenic changes, which can reduce vaccine efficacy. Therefore, it is essential to develop universal vaccines that target immunodominant epitopes derived from conserved regions of the influenza virus, enabling cross-protection among different virus variants. The internal proteins of the influenza virus serve as ideal targets for universal vaccines. These internal proteins are presented by MHC class I molecules on Ag-presenting cells, such as dendritic cells, and recognized by CD8 T cells, which elicit CD8 T cell responses, reducing the likelihood of disease and influenza viral spread by inducing virus-infected cell apoptosis. In this review, we highlight the importance of CD8 T cell-mediated immunity against influenza viruses and that of viral epitopes for developing CD8 T cell-based influenza vaccines.

11.
J Am Geriatr Soc ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38979845

RESUMO

BACKGROUND: Sleep aids are commonly prescribed to treat sleep disturbance, a modifiable risk factor for postoperative delirium in older patients. The use of melatonin receptor agonists in the postoperative period has been increasing. The comparative safety of melatonin receptor agonists, zolpidem, and temazepam remains uncertain. METHODS: This retrospective study included 22,083 patients ≥65 years old who initiated melatonin receptor agonists, zolpidem, or temazepam after major surgery in the Premier Healthcare Database 2009-2018. We performed propensity score-based overlap weighting and estimated the risk ratio (RR) and risk difference (RD) of postoperative delirium as the primary outcome and a composite of delirium or new antipsychotic initiation, pneumonia, and in-hospital mortality as secondary outcomes. RESULTS: The mean age of the study population was 78 (SD, 7) years and 50% were female. There was no significant difference in the risk of postoperative delirium among patients treated with melatonin receptor agonists (3.4%, reference group), zolpidem (2.9%; RR [95% CI], 0.9 [0.7-1.2]; RD [95% CI] per 100 persons, -0.3 [-1.1 to 0.6]), and temazepam (3.1%; 0.9 [0.7-1.1]; RD [95% CI] per 100 persons, -0.5 [-1.2 to 0.3]). The risks of delirium or new antipsychotic initiation, pneumonia, and in-hospital mortality were also similar among all groups. CONCLUSIONS: Melatonin receptor agonists were not associated with a lower risk of postoperative delirium and other adverse outcomes compared with zolpidem and temazepam in older adults after major surgery.

12.
Cells ; 13(12)2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38920659

RESUMO

Recent emerging studies have demonstrated numerous critical roles of exosomes in cell-to-cell signaling. We investigated exosomes in the aqueous humor of glaucoma patients and controls and compared their characteristics with other biomarkers such as cytokines. Glaucoma patients exhibited higher exosome particle counts and smaller sizes compared to controls. Higher exosome density was correlated with more severe visual field loss. Conversely, concentrations of aqueous humor cytokines, particularly PD-L1, were primarily associated with intraocular pressure, and none of the cytokines showed a significant association with visual field damage. This may reflect the characteristics of exosomes, which are advantageous for crossing various biological barriers. Exosomes may contain more information about glaucoma functional damage occurring in the retina or optic nerve head. This highlights the potential importance of exosomes as signaling mediators distinct from other existing molecules.


Assuntos
Humor Aquoso , Biomarcadores , Citocinas , Exossomos , Glaucoma , Humanos , Humor Aquoso/metabolismo , Exossomos/metabolismo , Biomarcadores/metabolismo , Glaucoma/metabolismo , Glaucoma/patologia , Citocinas/metabolismo , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Pressão Intraocular , Estudos de Casos e Controles
13.
Cells ; 13(12)2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38920673

RESUMO

In the context of glaucoma, intraocular pressure (IOP) and age are recognized as the primary factors contributing to its onset and progression. However, significant reductions in IOP fail to completely halt its advancement. An emerging body of literature highlights the role of neuroinflammation in glaucoma. This study aimed to explore Bromfenac's anti-inflammatory properties in mitigating neuroinflammation associated with glaucoma using an ischemia-reperfusion (IR) glaucoma model. Bromfenac's impact on microglia and astrocytes under pressure was assessed via Western blotting and an enzyme-linked immunosorbent assay. Immunohistochemical staining was used to evaluate glial activation and changes in inflammatory marker expression in the IR model. Bromfenac led to the downregulation of inflammatory markers, which were elevated in the conditions of elevated pressure, and necroptosis markers were downregulated in astrocytes. In the IR model, elevated levels of GFAP and Iba-1 indicated glial activation. Following Bromfenac administration, levels of iNOS, COX-2, and PGE2-R were reduced, suggesting a decrease in neuroinflammation. Furthermore, Bromfenac administration in the IR model resulted in the improved survival of retinal ganglion cells (RGCs) and preservation of retinal function, as demonstrated by immunohistochemical staining and electroretinography. In summary, Bromfenac proved effective in diminishing neuroinflammation and resulted in enhanced RGC survival.


Assuntos
Astrócitos , Benzofenonas , Bromobenzenos , Modelos Animais de Doenças , Glaucoma , Traumatismo por Reperfusão , Bromobenzenos/farmacologia , Bromobenzenos/uso terapêutico , Animais , Benzofenonas/farmacologia , Benzofenonas/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/complicações , Glaucoma/tratamento farmacológico , Glaucoma/patologia , Glaucoma/complicações , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Astrócitos/patologia , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/patologia , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/patologia , Células Ganglionares da Retina/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Masculino , Pressão Intraocular/efeitos dos fármacos , Ratos
14.
Arthroscopy ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38925233

RESUMO

PURPOSE: To investigate the effectiveness of bursal acromial resurfacing (acromiograft) on acromiohumeral distance, subacromial contact area, and pressure in a cadaveric model of massive rotator cuff tear. METHODS: Eight fresh-frozen cadaveric shoulders were tested using a customized shoulder testing system. Humeral head translation, subacromial contact pressure, and the subacromial contact area were evaluated across four conditions: (1) intact shoulder; (2) simulated massive rotator cuff tear; (3) 3-mm acromiograft condition; (4) 6-mm acromiograft condition. The acromiografts were simulated using Teflon and a reported technique. The values were measured at 0°, 20°, and 40° abduction and 0°, 30°, 60°, and 90° external rotation (ER) for each abduction status. RESULTS: Compared with a massive cuff tear, the 6-mm acromiograft significantly reduced the superior translation of the humeral head at all abduction/ER angles (P<0.05). The 3-mm acromiograft also decreased superior translation of the humeral head compared to massive cuff tear, but not all differences were significant. The 3- and 6-mm acromiografts significantly decreased the subacromial contact pressure and increased the subacromial contact area in almost all positions (P<0.05). The 3-mm acromiograft maintained biomechanical properties similar to the intact condition, whereas the 6-mm acromiograft increased the contact area. CONCLUSIONS: This biomechanical study demonstrated that both 3- and 6- mm acromiografts using Teflon in a cadaveric model of a massive cuff tear resulted in recentering of the superiorly migrated humeral head, increased the subacromial contact area, and decreased the subacromial contact pressure. The 3- mm graft was sufficient for achieving the intended therapeutic effects. CLINICAL RELEVANCE: The acromiograft can normalize altered biomechanics and may aid the treatment of massive cuff tears. As grafting the acromion's undersurface is new with limited clinical outcomes, further observation is crucial. Using Teflon instead of ADM allograft for bursal acromial resurfacing could yield different results, requiring careful interpretation.

15.
J Craniofac Surg ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38934651

RESUMO

The aim of this study is to analyze the process of metamorphosis of a tall and ugly woman through plastic surgery as depicted in The Life and Loves of a She-Devil (1983) of Fay Weldon. The process of plastic surgeries and the psychology of the protagonist of this novel were analyzed. A highly unattractive woman (Ruth, 185 cm) takes revenge on her husband (Bobbo, 175 cm) and his attractive lover (Mary Fisher, 160 cm). To transform her appearance, Ruth remodels her jaw, has her teeth extracted (2-jaw surgery or facial contouring surgery), straightens and trims her nose (corrective rhinoplasty), flattens her cheekbones (reduction malarplasty), reduces her breast size (reduction mammoplasty), and shortens both her arms and legs (limb reduction surgery). Following the series of surgeries, Ruth ultimately made herself look identical to Mary Fisher, her husband's lover. She believes her inadequacies stem from her body's failure to meet societal beauty standards, prompting her decision to "remake" herself. She declares, "I will be what I want, not what God ordained." Ruth's aspiration is not to acquire a new face but to attain the face of Mary Fisher. When confronted with pain and harm, Ruth does not waver but acknowledges it. "Of course it hurts. Andersen's little mermaid wanted legs instead of a tail. And, like her, I welcome it. I don't complain." In this study, we derived insights into why patients who want to change their entire bodies undergo plastic surgery, what these patients really want, and patients' attitudes toward the pain caused by surgical procedures.

16.
Anal Chem ; 96(25): 10246-10255, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38858132

RESUMO

Hypoxia is a representative tumor characteristic associated with malignant progression in clinical patients. Engineered in vitro models have led to significant advances in cancer research, allowing for the investigation of cells in physiological environments and the study of disease mechanisms and processes with enhanced relevance. In this study, we propose a U-shape pillar strip for a 3D cell-lumped organoid model (3D-COM) to study the effects of hypoxia on lung cancer in a high-throughput manner. We developed a U-pillar strip that facilitates the aggregation of PDCs mixed with an extracellular matrix to make the 3D-COM in 384-plate array form. The response to three hypoxia-activated prodrugs was higher in the 3D-COM than in the 2D culture model. The protein expression of hypoxia-inducible factor 1 alpha (HIF-1α) and HIF-2α, which are markers of hypoxia, was also higher in the 3D-COM than in the 2D culture. The results show that 3D-COM better recapitulated the hypoxic conditions of lung cancer tumors than the 2D culture. Therefore, the U-shape pillar strip for 3D-COM is a good tool to study the effects of hypoxia on lung cancer in a high-throughput manner, which can efficiently develop new drugs targeting hypoxic tumors.


Assuntos
Ensaios de Triagem em Larga Escala , Neoplasias Pulmonares , Organoides , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Organoides/metabolismo , Organoides/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia Celular , Técnicas de Cultura de Células em Três Dimensões , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo
17.
Allergy Asthma Immunol Res ; 16(3): 253-266, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38910283

RESUMO

PURPOSE: Severe asthma is associated with high morbidity and healthcare utilization; however, treatment options for these patients are limited. This study aimed to determine the therapeutic effects of biologics in clinical practice. METHODS: This multicenter, retrospective cohort study included 136 patients who received biologics for at least 4 months between September 2017 and July 2022 at 25 medical centers affiliated with the Korean Severe Asthma Registry (KoSAR). The study evaluated the treatment effects, including acute exacerbation rates, maintenance of oral corticosteroid dosages, lung function, quality of life, blood eosinophil count, and fractional exhaled nitric oxide (FeNO) levels, by comparing measurements before and after 4 months of biologic treatment. Responses for each medication was evaluated based on the Global Evaluation of Treatment Effectiveness score, and any adverse reactions were summarized. RESULTS: With the administration of biologics over the course of 4 months, there was a reduction in asthma acute exacerbations, a significant improvement in lung function, and a significant decrease in daily maintenance dose of oral steroid. Blood eosinophil counts decreased in the mepolizumab and reslizumab groups, while FeNO levels decreased only in the dupilumab group. The Asthma Control Test, Quality of Life Questionnaire for Adult Korean Asthmatics, and the EuroQol-visual analogue scale scores showed a significant improvement. Most patients (80.15%) responded to the biologic treatment. Meanwhile, non-responders often had chronic rhinosinusitis as a comorbidity, exhibited lower lung function, and required higher doses of oral steroids. No severe adverse events were reported. CONCLUSIONS: Biologics are highly effective in Korean patients with Type 2 severe asthma, significantly reducing acute exacerbation rates and doses of oral corticosteroids, while also improving lung function. Therefore, it seems beneficial to administer biologics without any restrictions to patients exhibiting Type 2 severe asthma.

18.
Allergy Asthma Immunol Res ; 16(3): 279-290, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38910285

RESUMO

PURPOSE: This study investigated the impact of aeroallergens on the development and progression of chronic rhinosinusitis (CRS), with a focus on the specific associations between aeroallergens and CRS according to allergen type, number, and extent of sensitization. METHODS: The medical records of 256 CRS patients were retrospectively analyzed. All were divided into nonallergic, house dust mite (HDM)-allergic, pollen-allergic, and double allergic groups via specific immunoglobulin E (IgE) testing. Clinical characteristics, computed tomography (CT) scores, olfactory functions, and demographic data were compared. Correlation analysis was performed to explore the relationships between the extent of allergen sensitization and CRS severity. Binary logistic regression analysis was used to identify risk factors for hyposmia and anosmia. RESULTS: The allergic group exhibited higher total CT scores than the nonallergic group (P = 0.001). Sensitivity to HDM or pollen allergens alone was not significantly associated with increased CRS severity. No significant differences were observed between the effects of HDM and pollen allergens on CRS severity. However, the double allergic group exhibited significantly higher CT scores (P < 0.001, < 0.001, and 0.003) than the other groups. Although the prevalence rates of anosmia and hyposmia were notably higher in the double allergic group, the difference was not statistically significant. The maximum specific IgE levels to HDM and pollen allergens positively correlated with the CT scores (P = 0.001 and 0.001, respectively). CONCLUSIONS: Allergen sensitization, particularly to multiple common allergens, contributed to CRS severity. CRS patients sensitized to both HDM and pollen allergens tended to experience the diminished olfactory function. These findings underscore the importance of considering the allergen sensitization pattern when assessing CRS severity and its potential progression.

19.
Sci Rep ; 14(1): 14144, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898029

RESUMO

We propose a topological coherent perfect absorber that enables almost ideal performance with remarkably compact device footprint and tight incident beams. The proposed structure is based on a topological junction of two guided-mode-resonance gratings. The structure provides robust systematic ways of remarkably tight lateral confinement of the absorbing resonance mode and near-perfect mode-match to arbitrary incident beams, which are unavailable with the conventional approaches. We demonstrate an exemplary amorphous Si thin-film structure that enables near-perfect absorptance modulation between 1.7 and 99% with device footprint width of 30-µm and 10-µm-wide incident Gaussian beams. Therefore, our proposed approach greatly improves practicality of guided-mode-resonance coherent perfect absorbers.

20.
Lung ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847887

RESUMO

PURPOSE: Symptoms are important components in determining asthma control and in the adjustment of treatment levels. However, clinical relevance of cough in severe asthma is not well-understood. This study aimed to evaluate the severity and association of cough with patient-reported outcomes (PROs) in patients with severe asthma. METHODS: This study analyzed cross-sectional data from the Korean Severe Asthma Registry. The severity of coughing and wheezing symptoms was assessed using a Visual Analog Scale (VAS) ranging from 0 to 100 for each symptom. Additionally, PROs included the Asthma Control Test (ACT), the Severe Asthma Questionnaire (SAQ), and the EuroQoL 5-Dimension (EQ-5D) index. Multivariate linear regression analysis was employed to explore the relationship between cough severity and other PRO scores. RESULTS: A total of 498 patients with severe asthma (age: 57.9 ± 13.1 years, females: 60.2%) were analyzed. The cough VAS score was higher than the wheeze score (median 30, [interquartile range 10-50] vs. 20 [0-50]; P < 0.001). Additionally, 22.5% of patients ranked in a higher tertile for cough severity compared to wheezing, while 18.5% ranked higher for wheezing severity than cough. Significant correlations were observed between cough and wheeze VAS scores (r = 0.61, P < 0.05) and between each symptom's VAS score and the SAQ (cough: r = -0.41, P < 0.001; wheeze: r = -0.52, P < 0.001), ACT scores (cough: r = -0.50, P < 0.001; wheeze: r = -0.63, P < 0.001) and EQ-5D index (cough: r = -0.40, P < 0.001; wheeze: r = -0.45, P < 0.001). In univariate regression analysis, the cough VAS score had weaker descriptive power (R2) values than the wheeze VAS score in relation to the PRO measures. Nevertheless, cough severity remained significantly associated with ACT, SAQ scores and EQ-5D index in multivariate analyses adjusted for wheeze severity and other confounders. CONCLUSION: Cough frequently presents as a severe symptom in patients with severe asthma and could have distinct impact on asthma control and quality of life.

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