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1.
Disabil Rehabil Assist Technol ; : 1-6, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39162349

RESUMO

This study investigated the effects of using the LiftCar-150 track-based stair-climbing robot on muscle activity, usability, and psychological anxiety. While stair-climbing robots enhance mobility for individuals with physical disabilities, existing research has predominantly focused on engineering perspectives, with limited attention to user-centered outcomes. Ten healthy participants and an 80 kg dummy rider completed stair-climbing tasks at slow (5 m/min) and fast (7 m/min) speeds. Muscle activity in the middle trapezius (MT), erector spinae (ES), multifidus (MF), gluteus maximus (Gmax), gluteus medius (Gmed), and anterior deltoid (AD) muscles was recorded by electromyography. Usability was evaluated in terms of safety, efficiency, and satisfaction using a 5-point Likert scale, while psychological anxiety was assessed with a visual analog scale (VAS) ranging from 0 to 10. Results showed that during stair ascent, activities of the back extensors (ES and MF) and gluteus muscles (Gmax and Gmed) significantly increased compared to descent, while anterior deltoid activity was higher during descent. Usability scores averaged 4.05 for stability, 4.1 for efficiency, and 3.7 for satisfaction. Perceived psychological anxiety scores were 4.2 ± 0.3 and 5.4 ± 0.5 at slow speed, and 3.5 ± 0.2 and 5.7 ± 0.4 at fast speed during ascent and descent, respectively. While operators recognized the robot's stability and efficiency, satisfaction levels were neutral, and specific muscle activation was increased. These findings provide essential insights into optimizing the design and usability of stair-climbing robots to better address user needs.


The proposed user-centered approach in this study can be used to improve performance and user satisfaction of a wide range of mobility device.To reduce extensor muscle activity caused by forward bending during initial stair climbing, it is necessary to modify the fixed handle design to allow adjustable handle height.Additionally, exploring options for weight reduction and repositioning the power button may further optimize the LiftCar-150, contributing to increased usability and satisfaction for operators.

2.
Sci Total Environ ; : 175472, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39142414

RESUMO

Acetaminophen (APAP) is a well-known type of over-the-counter painkiller and is frequently found in surface waterbodies, causing hepatotoxicity and skin irritation. Due to its persistence and chronic effects on the environment, innovative solutions must be provided to decompose APAP effectively. Successfully, innovative catalysts of tungsten-modified iron oxides (TF) were developed via a combustion method and thoroughly characterized using SEM, TEM, XRD, XPS, a porosimetry analysis, Mössbauer spectroscopy, VSM magnetometry, and EPR. With the synthesis method, tungsten was successfully incorporated into iron oxides to form ferrites and other magnetic iron oxides with a high porosity of 19.7 % and a large surface area of 29.5 m2/g. Also, their catalytic activities for APAP degradation by activating peroxymonosulfate (PMS) were evaluated under various conditions. Under optimal conditions, TF 2.0 showed the highest APAP degradation of 95 % removal with a catalyst loading of 2.0 g/L, initial APAP concentration of 5 mg/L, PMS 6.5 mM, and pH 2.15 at room temperature. No inhibition by solution pHs, alkalinity, and humic acid was observed for APAP degradation. The catalysts also showed chemical and mechanical stability, achieving 100 % degradation of 1 mg/L APAP during reusability tests with three consecutive experiments. These results show that TFs can effectively degrade persistent contaminants of emerging concern in water, offering an impactful contribution to wastewater treatment to protect human health and the ecosystem.

3.
J Orthop Surg Res ; 19(1): 458, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39095797

RESUMO

BACKGROUND: Preventing severe arthrogenic muscle inhibition (AMI) after knee injury is critical for better prognosis. The novel Sonnery-Cottet classification of AMI enables the evaluation of AMI severity but requires validation. This study aimed to investigate the electromyography (EMG) patterns of leg muscles in the examination position from the classification during isometric contraction to confirm its validity. We hypothesised that the AMI pattern, which is characterised by quadriceps inhibition and hamstring hypercontraction, would be detectable in the supine position during isometric contraction. METHODS: Patients with meniscal or knee ligament injuries were enrolled between August 2023 and May 2024. Surface EMG was assessed during submaximal voluntary isometric contractions (sMVIC) at 0° extension in the supine position for the vastus medialis (VM) and vastus lateralis (VL) muscles and at 20° flexion in the prone position for the semitendinosus (ST) and biceps femoris (BF) muscles. Reference values for normalisation were obtained from the EMG activity during the gait of the uninjured leg. The Kruskal-Wallis test was used to compare the activation patterns of the muscle groups within the same leg, and the post-hoc tests were conducted using the Mann-Whitney U test and Bonferroni correction. RESULTS: Electromyographic data of 40 patients with knee injuries were analyzed. During sMVIC, the extensor and flexor muscles of the injured leg showed distinct behaviours (P < 0.001), whereas the uninjured side did not (P = 0.144). In the injured leg, the VM differed significantly from the ST (P = 0.018), and the VL differed significantly from the ST and BF (P = 0.001 and P = 0.026, respectively). However, there were no statistically significant differences within the extensor muscle groups (VM and VL, P = 0.487) or flexor muscle groups (ST and BF, P = 0.377). CONCLUSION: AMI was detectable in the examination position suggested by the Sonnery-Cottet classification. The flexor and extensor muscles of the injured leg exhibited distinct activation behaviours, with inhibition predominantly occurring in the quadriceps muscles, whereas the hamstrings showed excitation.


Assuntos
Eletromiografia , Contração Isométrica , Músculo Quadríceps , Humanos , Eletromiografia/métodos , Músculo Quadríceps/fisiopatologia , Músculo Quadríceps/fisiologia , Contração Isométrica/fisiologia , Masculino , Estudos Transversais , Adulto , Feminino , Decúbito Dorsal/fisiologia , Traumatismos do Joelho/fisiopatologia , Adulto Jovem , Exame Físico/métodos , Pessoa de Meia-Idade , Estudos de Viabilidade
4.
Int J Pharm ; 662: 124519, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39067551

RESUMO

The use of messenger RNA (mRNA) as a cancer vaccine and gene therapy requires targeted vehicle delivery to the site of disease. Here, we designed a mRNA-encapsulating lipid nanoparticle (LNP) conjugated with anti-programmed death-ligand 1 (PD-L1) DNA aptamer that delivers mRNA encoding a tumor suppressor gene, namely phosphatase and tensin homolog (PTEN), to castration-resistant prostate cancer (CRPC) cells expressing PD-L1 on the cell surface. The DNA aptamer-conjugated LNP-based mRNA delivery system (Apt-LNP[PTEN mRNA]) mediated efficient mRNA delivery and transfection in CRPC cells than LNPs without targeting ligands. Cancer-targeted PTEN mRNA delivery using Apt-LNPs achieved significantly higher PTEN expression via aptamer-mediated endocytosis in target cancer cells compared with non-targeted LNP delivery, resulting in significant downregulation of AKT phosphorylation. This enhanced PI3K/AKT pathway regulation, and in turn reduced cell migration after two days along with a 70 % decrease in cell viability, leading to effective apoptotic cell death. In a CRPC xenograft model, Apt-LNP[PTEN mRNA] led to an approximate 60 % reduction in tumor growth, which was attributable to the effective PTEN restoration and PI3K/AKT signaling pathway regulation. PTEN expression was significantly enhanced in CRPC tumor tissues, which abolished cancer cell tumorigenicity. These findings demonstrated the potential of Apt-LNPs for targeted mRNA delivery to cancer cells, thus providing a promising tool for targeted mRNA delivery to a range of cancers and tissues using a conventional LNP systems.

5.
J Clin Med ; 13(12)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38929964

RESUMO

Background/Objectives: This study aimed to assess the effectiveness of bi-monthly brolucimumab treatment in patients with neovascular age-related macular degeneration (nAMD) refractory to monthly aflibercept treatment. Methods: A retrospective chart review included 32 eyes of patients with refractory nAMD who switched from monthly intravitreal aflibercept treatment to bi-monthly intravitreal brolucizumab treatment. This study evaluated changes in visual acuity (VA), intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED), and central macular thickness (CMT), at specific times as follows: baseline before switching (T0), 2 months after switching (T1), 4 months after switching (T2), and 6 months after switching (T3). Results: The mean best-corrected visual acuity (BCVA) did not significantly change across all time points (0.52 ± 0.12, 0.48 ± 0.27, 0.48 ± 0.28, and 0.50 ± 0.27 logarithms of the minimum angle of resolution in T0, T1, T2, and T3, respectively). CMT significantly decreased after additional brolucizumab injections compared to the baseline (218.2 ± 48.6 and 207.9 ± 49.8 µm, respectively; p = 0.001). The PED height also significantly decreased from 251.0 ± 165.4 to 154.4 ± 115.65 µm (p < 0.001), with complete resolution in nine patients (28%). The mean subfoveal choroidal thickness (SFCT) before brolucizumab treatment was 262.8 ± 79.7 µm, which decreased to 233.0 ± 71.2 µm (p = 0.001) after the first injection. The final SFCT also significantly decreased after additional brolucizumab injections compared to the baseline SFCT (p = 0.012). Conclusions: Bi-monthly brolucizumab treatment proves effective for patients refractory to monthly fixed aflibercept, resulting in positive anatomical changes without significant deterioration in visual acuity. This approach provides a promising prognosis while reducing the treatment burden on refractory patients.

6.
PLoS One ; 19(6): e0304785, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38941283

RESUMO

In this study, we employed various machine learning models to predict metabolic phenotypes, focusing on thyroid function, using a dataset from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012. Our analysis utilized laboratory parameters relevant to thyroid function or metabolic dysregulation in addition to demographic features, aiming to uncover potential associations between thyroid function and metabolic phenotypes by various machine learning methods. Multinomial Logistic Regression performed best to identify the relationship between thyroid function and metabolic phenotypes, achieving an area under receiver operating characteristic curve (AUROC) of 0.818, followed closely by Neural Network (AUROC: 0.814). Following the above, the performance of Random Forest, Boosted Trees, and K Nearest Neighbors was inferior to the first two methods (AUROC 0.811, 0.811, and 0.786, respectively). In Random Forest, homeostatic model assessment for insulin resistance, serum uric acid, serum albumin, gamma glutamyl transferase, and triiodothyronine/thyroxine ratio were positioned in the upper ranks of variable importance. These results highlight the potential of machine learning in understanding complex relationships in health data. However, it's important to note that model performance may vary depending on data characteristics and specific requirements. Furthermore, we emphasize the significance of accounting for sampling weights in complex survey data analysis and the potential benefits of incorporating additional variables to enhance model accuracy and insights. Future research can explore advanced methodologies combining machine learning, sample weights, and expanded variable sets to further advance survey data analysis.


Assuntos
Aprendizado de Máquina , Fenótipo , Glândula Tireoide , Humanos , Glândula Tireoide/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Inquéritos Nutricionais , Testes de Função Tireóidea , Curva ROC , Redes Neurais de Computação
7.
J Exp Psychol Gen ; 153(7): 1920-1937, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38856918

RESUMO

Commencement speakers, business leaders, and the popular press tell us that failure has at least one benefit: It fuels success. Does it? Across 11 studies, including a field study of medical professionals, predictors overestimated the rate at which people course correct following failure (Studies 1-4). Predictors overestimated the likelihood that professionals who fail a professional exam (e.g., the bar exam, the medical boards) pass a retest (Studies 1a, 1b, and 2a), the likelihood that patients improve their health after a crisis (e.g., heart attack, drug overdose; Studies 2b and 6), and the probability, more generally, of learning from one's mistakes (Studies 3-5). This effect was specific to overestimating success following failure (Study 4) and erasing mention of an initial failure that had actually occurred corrected the problem (Studies 2a and 2b). The success overestimate was due, at least in part, to the belief that people attend to failure more than they do (Studies 5 and 6). Correcting this overestimate had policy implications. Citizens apprised of the sobering true rate of postfailure success increased their support for rehabilitative initiatives aimed at helping struggling populations (e.g., people with addiction, ex-convicts) learn from past mistakes (Studies 7a-7c). (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Assuntos
Fracasso Acadêmico , Humanos , Fracasso Acadêmico/psicologia
8.
Bone Res ; 12(1): 29, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38744829

RESUMO

Mature osteoclasts degrade bone matrix by exocytosis of active proteases from secretory lysosomes through a ruffled border. However, the molecular mechanisms underlying lysosomal trafficking and secretion in osteoclasts remain largely unknown. Here, we show with GeneChip analysis that RUN and FYVE domain-containing protein 4 (RUFY4) is strongly upregulated during osteoclastogenesis. Mice lacking Rufy4 exhibited a high trabecular bone mass phenotype with abnormalities in osteoclast function in vivo. Furthermore, deleting Rufy4 did not affect osteoclast differentiation, but inhibited bone-resorbing activity due to disruption in the acidic maturation of secondary lysosomes, their trafficking to the membrane, and their secretion of cathepsin K into the extracellular space. Mechanistically, RUFY4 promotes late endosome-lysosome fusion by acting as an adaptor protein between Rab7 on late endosomes and LAMP2 on primary lysosomes. Consequently, Rufy4-deficient mice were highly protected from lipopolysaccharide- and ovariectomy-induced bone loss. Thus, RUFY4 plays as a new regulator in osteoclast activity by mediating endo-lysosomal trafficking and have a potential to be specific target for therapies against bone-loss diseases such as osteoporosis.


Assuntos
Endossomos , Lisossomos , Osteoclastos , Animais , Feminino , Camundongos , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Reabsorção Óssea/genética , Catepsina K/metabolismo , Catepsina K/genética , Diferenciação Celular , Endossomos/metabolismo , Deleção de Genes , Lisossomos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteoclastos/metabolismo , Transporte Proteico , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas rab de Ligação ao GTP/genética , proteínas de unión al GTP Rab7 , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismo
9.
Small ; : e2402341, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38795003

RESUMO

Poly(3,4-ethylenedioxythiophene) (PEDOT), particularly in its complex form with poly(styrene sulfonate) (PEDOT:PSS), stands out as a prominent example of an organic conductor. Renowned for its exceptional conductivity, substantial light transmissibility, water processability, and remarkable flexibility, PEDOT:PSS has earned its reputation as a leading conductive polymer. This study explores the unique effects of two additives, Bisphenol A diglycidyl ether (DGEBA) and Dimethyl sulfoxide (DMSO), on the PSS component of PEDOT:PSS films are shown. Both additives induce grain size growth, while DGEBA makes the PEDOT:PSS layer hydrophobic, which acts as a passivation to protect the perovskite layer, which is vulnerable to moisture. The other additive, DMSO, separates the PSS groups, resulting in increased conductivity through the free movement of holes. With these multi-modified p-type PEDOT:PSS, the ITO/M-PEDOT:PSS/Perovskite/PCBM/Ag structured reverse structure solar cell has improved the power conversion efficiency (PCE) from 15.28% to 17.80% compared to the control cell with conventional PEDOT:PSS. It also maintains 90% for 500 h at 60 °C and 300 h at 1 sun illuminating conditions.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38620035

RESUMO

CONTEXT: Thyroid hormones are essential for energy metabolism related to thermogenesis and oxygen consumption. OBJECTIVE: This study evaluated the potential association of thyroid function including thyroid peroxidase antibodies (TPOAb) with physical activity in nationally representative data. DESIGN/SETTING/PARTICIPANTS: This retrospective cohort study used data from the Korean National Health and Nutrition Examination Survey between 2013 and 2015. Physical activity (PA) was assessed using metabolic equivalents based on the validated Korean version of the International Physical Activity Questionnaire Short Form. PA level was categorized into 3 groups of high, moderate, and low. Participants with abnormal thyroid function test, restricted activity, or previous history of thyroid disease were excluded in the study. RESULTS: A total of 5372 participants was finally selected. The free T4 level was lowest in the low PA group, while TSH was not significantly different among the groups. TPOAb titers increased in the following order: moderate PA, low PA, and high PA. After adjustment for confounding factors, moderate PA was associated with a high T4 level and a decrease in TSH and TPOAb with significance. However, there were no significant changes in free T4, TSH, or TPOAb titer in the high PA group. In a subanalysis, females with moderate PA showed a significant decrease in TSH and TPOAb. In both males and females, insulin sensitivity was increased with moderate PA. In obese participants, TSH negatively correlated with PA, and free T4 levels decreased in the low PA. The sensitivity to thyroid hormone did not differ in our study. CONCLUSION: The present study found an association between thyroid function and moderate PA. Therefore, moderate-intensity PA should be recommended to improve thyroid function.

11.
Microbes Infect ; : 105319, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38447861

RESUMO

Recent advances in organoid and organ-on-chip (OoC) technologies offer an unprecedented level of tissue mimicry. These models can recapitulate the diversity of cellular composition, 3D organization, and mechanical stimulation. These approaches are intensively used to understand complex diseases. This review focuses on the latest advances in this field to study host-microorganism interactions.

12.
Sci Total Environ ; 921: 171016, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38369142

RESUMO

Climate change can affect precipitation patterns, temperature, and the hydrological cycle, consequently influencing the dynamics of nitrogen (N) within aquatic ecosystems. In this study, multiple stable isotopes (15N-NO3/18O-NO3 and 2H-H2O/18O-H2O) were used to investigate the N sources and flowpath within the Bogang stream in South Korea. Within the vicinity of the stream with complex land use where various N sources were present, four end-members (rainfall, soil, sewage, and livestock) were sampled and examined. Consequently, spatial-temporal variations of the N sources were observed dependent on the type of land use. During the dry season, sewage accounted for the dominant N source, ranging from 62.2 % to 80.2 %. In contrast, nonpoint sources increased significantly across most sites during the wet season (10.3-41.6 % for soil; 6.3-35.2 % for livestock) compared to the dry season (7.7-28.5 % for soil; 6-13.2 % for livestock). However, sewage (78.7 %) remains dominant, representing the largest ratio at the site downstream of the wastewater treatment plant during the wet season. This ratio showed a notable difference from the calculated N loading ratio of 52.2 %, especially for livestock. This suggests that a significant potential for N legacy effects, given that groundwater flow is likely to be the primary hydrological pathway delivering N to rivers. This study will help to develop water resource management strategies by understanding how the interaction between N sources and hydrological process responds to climate change within sub-basins.

13.
Vet Sci ; 11(2)2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38393114

RESUMO

With the increase in the number of households raising dogs and the reports of human-to-dog transmission of oral bacteria, concerns about dogs' oral health and the need for oral hygiene management are increasing. In this study, the owners' perceptions about their dogs' oral health and the frequency of oral hygiene were determined along with the analysis of dog dental plaque bacteria through metagenomic amplicon sequencing so as to support the need for oral hygiene management for dogs. Although the perception of 63.2% of the owners about their dogs' oral health was consistent with the veterinarian's diagnosis, the owners' oral hygiene practices regarding their dogs were very poor. The calculi index (CI) and gingiva index (GI) were lower in dogs who had their teeth brushed more than once a week (57.89%) than in dogs brushed less than once a month (42.10%); however, the difference was nonsignificant (CI: p = 0.479, GI: p = 0.840). Genomic DNA was extracted from dental plaque bacteria removed during dog teeth scaling, and metagenomic amplicons were sequenced. The 16S amplicons of 73 species were identified from among the plaque bacteria of the dogs. These amplicons were of oral disease-causing bacteria in humans and dogs. The 16S amplicon of Streptococcus mutans matched that of the human S. mutans, with type c identified as the main serotype. This result suggests that human oral bacteria can be transmitted to dogs. Therefore, considering the high frequency of contact between dogs and humans because of communal living and the current poor oral health of dogs, owners must improve the oral hygiene management of their dogs.

15.
Biomed Eng Lett ; 14(1): 13-21, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38186957

RESUMO

Alzheimer's disease (AD) has a detrimental impact on brain function, affecting various aspects such as cognition, memory, language, and motor skills. Previous research has dominantly used electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) to individually measure brain signals or combine the two methods to target specific brain functions. However, comprehending Alzheimer's disease requires monitoring various brain functions rather than focusing on a single function. This paper presents a comprehensive research setup for a monitoring platform for AD. The platform incorporates a 32-channel dry electrode EEG, a custom-built four-channel fNIRS, and gait monitoring using a depth camera and pressure sensor. Various tasks are employed to target multiple brain functions. The paper introduced the detailed instrumentation of the fNIRS system, which measures the prefrontal cortex, outlines the experimental design targeting various brain functioning programmed in BCI2000 for visualizing EEG signals synchronized with experimental stimulation, and describes the gait monitoring hardware and software and protocol design. The ultimate goal of this platform is to develop an easy-to-perform brain and gait monitoring method for elderly individuals and patients with Alzheimer's disease. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-023-00306-7.

16.
BMC Ophthalmol ; 24(1): 25, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38243166

RESUMO

BACKGROUND: Triamcinolone acetonide (TA) is administered as an intravitreal or posterior sub-Tenon's capsule injection, as treatment for diabetic macular edema (DME). The intravitreal use of TA is limited because commercially available triamcinolone acetonide contains benzyl alcohol, a neurotoxic preservative. Few studies have compared effects of preservative-free intravitreal TA (IVTA) and posterior sub-Tenon capsule TA (STTA) injections for DME. Thus, herein, we compared the effectiveness of preservative-free IVTA and STTA for treatment of bevacizumab-resistant DME. METHODS: In this retrospective cohort study, bevacizumab-resistant DME was defined as a lack of response to at least three consecutive intravitreal bevacizumab (IVB) injections. Changes in mean central macula thickness (CMT), best-corrected visual acuity (BCVA), and intraocular pressure (IOP) between IVTA and STTA groups were compared at baseline and at 1, 2, and 3 months after treatment. RESULTS: Forty eyes from 40 patients were included in this study. In the IVTA group, the mean CMT improved significantly from 400.2 ± 144.42 µm at baseline to 288.35 ± 151.74 µm at 3 months after treatment (p = 0.01). Similarly, in the STTA group, the mean CMT improved significantly from 446.65 ± 120.74 µm at baseline to 382.9 ± 113.58 µm at 3 months after treatment (p = 0.009). The mean BCVA of the IVTA group also showed improvement, decreasing from 0.75 ± 0.55 logarithm of the minimum angle of resolution (logMAR) at baseline to 0.625 ± 0.50 logMAR at 3 months after treatment (p = 0.089). Similarly, the mean BCVA of the STTA group improved, from 0.6 ± 0.36 logMAR at baseline to 0.54 ± 0.35 logMAR at 3 months after treatment (p = 0.094). CONCLUSION: Given that IVTA and STTA demonstrated statistically equivalent anatomical and functional effects in patients with bevacizumab-resistant DME, the less invasive STTA may be considered the preferred treatment approach for the management of bevacizumab-resistant DME. TRIAL REGISTRATION: Retrospectively registered.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Humanos , Triancinolona Acetonida , Bevacizumab/uso terapêutico , Glucocorticoides , Retinopatia Diabética/complicações , Edema Macular/etiologia , Estudos Retrospectivos , Injeções Intravítreas , Resultado do Tratamento
17.
Nat Commun ; 15(1): 645, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245505

RESUMO

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is currently the leading cause of chronic liver disease worldwide. Metabolic Dysfunction-Associated Steatohepatitis (MASH), an advanced form of MASLD, can progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Based on recent findings by our team that liver 5HT2A knockout male mice suppressed steatosis and reduced fibrosis-related gene expression, we developed a peripheral 5HT2A antagonist, compound 11c for MASH. It shows good in vitro activity, stability, and in vivo pharmacokinetics (PK) in rats and dogs. Compound 11c also shows good in vivo efficacy in a diet-induced obesity (DIO) male mice model and in a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) male mice model, effectively improving histologic features of MASH and fibrosis. According to the tissue distribution study using [14C]-labeled 11c, the compound was determined to be a peripheral 5HT2A antagonist. Collectively, first-in-class compound 11c shows promise as a therapeutic agent for the treatment of MASLD and MASH.


Assuntos
Fígado Gorduroso , Neoplasias Hepáticas , Fenômenos Fisiológicos Musculoesqueléticos , Masculino , Camundongos , Animais , Cães , Ratos , Fígado Gorduroso/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Camundongos Knockout
18.
BMC Gastroenterol ; 24(1): 30, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212710

RESUMO

BACKGROUND: This study investigated the frequency of diabetic gastroparesis and associated risk factors in a real-world clinical setting. METHODS: This retrospective cross-sectional study included patients who underwent assessments of solid gastric emptying time (GET) by technetium-99 m scintigraphy between May 2019 and December 2020. We categorized patients into three groups according to gastric retention of technetium-99 m: rapid (< 65% at 1 h or < 20% at 2 h), normal (≤60% at 2 h and/or ≤ 10% at 4 h), and delayed (> 60% at 2 h and/or > 10% at 4 h). RESULTS: Patients with diabetes mellitus (DM) were more likely to show abnormal GET than those without DM (119 [70.8%] vs. 16 [44.4%]). The mean glycated A1c was 10.3% in DM patients. DM patients with normal GET were significantly younger (57.2 years, P = 0.044) than those with delayed (65.0 years) or rapid GET (60.2 years). Fasting glucose levels were the lowest in the normal GET group and the highest in the rapid GET group (delayed: 176.3 mg/dL, normal: 151.2 mg/dL, rapid: 181.0 mg/dL, P = 0.030). However, glycated A1c was not significantly different among the delayed, normal, and rapid GET groups in patients with DM. Patients with delayed and rapid GET showed a higher frequency of retinopathy (6.0 vs. 15.5%, P = 0.001) and peripheral neuropathy (11.3 vs. 24.4%, P = 0.001) than those with normal GET. In the multinomial logistic regression analysis, retinopathy demonstrated a positive association with delayed GET, while nephropathy showed a significant negative correlation. CONCLUSION: DM gastroparesis in the clinical setting was not uncommon. Abnormal GET, including delayed and rapid GET, was associated with DM retinopathy or peripheral neuropathy.


Assuntos
Diabetes Mellitus , Neuropatias Diabéticas , Gastroparesia , Doenças Retinianas , Tecnécio , Humanos , Gastroparesia/epidemiologia , Gastroparesia/etiologia , Esvaziamento Gástrico , Estudos de Coortes , Estudos Retrospectivos , Estudos Transversais , Neuropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/complicações , Doenças Retinianas/complicações , Diabetes Mellitus/epidemiologia
19.
STAR Protoc ; 5(1): 102773, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38103194

RESUMO

Here, we present a protocol for microinjection of bacteria into mouse small intestinal organoids that recapitulates the natural route of infection of intestinal epithelial cells from the intestinal lumen. We describe steps for visualizing bacteria-cell interactions by live imaging of infected organoids using light sheet microscopy. We then detail procedures for generating doxycycline-inducible expression of mutant proteins in organoids to study essential gene functions. The different techniques described in this protocol can be used independently as required. For complete details on the use and execution of this protocol, please refer to Kim et al. (2021).1.


Assuntos
Bactérias , Microscopia , Animais , Camundongos , Bactérias/genética , Comunicação Celular , Doxiciclina , Organoides
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