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1.
Int J Antimicrob Agents ; : 107300, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39173938

RESUMEN

OBJECTIVES: To investigate whether using the BioFire® FilmArray® Blood Culture Identification 2 panel (BCID2) leads to timely antimicrobial therapy and improves patient outcomes in critically ill patients with bloodstream infections (BSIs). METHODS: This retrospective observational study included patients with BSIs admitted to the intensive care unit from July 1, 2021, to August 31, 2023. Patients were divided into groups receiving appropriate or inappropriate antimicrobial therapy. Those receiving inappropriate therapy underwent adjustments using standard-of-care (SOC) testing or BCID2. Propensity score matching (PSM) was performed on the original cohort (Model 1) and a time-window bias-adjusted cohort (Model 2). Clinical impact of BCID2-guided antimicrobial adjustment was analyzed in both models. RESULTS: A total of 181 patients received inappropriate antimicrobial therapy, with 33 undergoing BCID2 testing and 148 undergoing SOC testing. Following PSM and time-window bias adjustment, 66 patients were analyzed in Model 1 and 46 patients in Model 2. BCID2 significantly reduced the median time to appropriate antimicrobial therapy (40.8 vs. 74.0 h in Model 1; 42.8 vs. 68.9 h in Model 2) and the day-28 mortality rate (27.8% vs. 77.1%, p < 0.001 in Model 1; 23.5% vs. 58.6%, p = 0.021 in Model 2). In multivariate regression analysis, BCID2-guided antimicrobial adjustment was an independent prognostic factor for day-28 mortality (adjusted odds ratio [aOR] 0.07 in Model 1 and aOR 0.12 in Model 2). CONCLUSION: BCID2-guided antimicrobial stewardship was associated with a shorter time to appropriate antimicrobial therapy and reduced day-28 mortality in critically ill patients with BSIs receiving inappropriate antimicrobial therapy.

2.
Mol Med ; 30(1): 125, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39152382

RESUMEN

BACKGROUND: Epimedin A (EA) has been shown to suppress extensive osteoclastogenesis and bone resorption, but the effects of EA remain incompletely understood. The aim of our study was to investigate the effects of EA on osteoclastogenesis and bone resorption to explore the corresponding signalling pathways. METHODS: Rats were randomly assigned to the sham operation or ovariectomy group, and alendronate was used for the positive control group. The therapeutic effect of EA on osteoporosis was systematically analysed by measuring bone mineral density and bone biomechanical properties. In vitro, RAW264.7 cells were treated with receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) to induce osteoclast differentiation. Cell viability assays, tartrate-resistant acid phosphatase (TRAP) staining, and immunofluorescence were used to elucidate the effects of EA on osteoclastogenesis. In addition, the expression of bone differentiation-related proteins or genes was evaluated using Western blot analysis or quantitative polymerase chain reaction (PCR), respectively. RESULTS: After 3 months of oral EA intervention, ovariectomized rats exhibited increased bone density, relative bone volume, trabecular thickness, and trabecular number, as well as reduced trabecular separation. EA dose-dependently normalized bone density and trabecular microarchitecture in the ovariectomized rats. Additionally, EA inhibited the expression of TRAP and NFATc1 in the ovariectomized rats. Moreover, the in vitro results indicated that EA inhibits osteoclast differentiation by suppressing the TRAF6/PI3K/AKT/NF-κB pathway. Further studies revealed that the effect on osteoclast differentiation, which was originally inhibited by EA, was reversed when the TRAF6 gene was overexpressed. CONCLUSIONS: The findings indicated that EA can negatively regulate osteoclastogenesis by inhibiting the TRAF6/PI3K/AKT/NF-κB axis and that ameliorating ovariectomy-induced osteoporosis in rats with EA may be a promising potential therapeutic strategy for the treatment of osteoporosis.


Asunto(s)
Diferenciación Celular , FN-kappa B , Osteoclastos , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Factor 6 Asociado a Receptor de TNF , Animales , Factor 6 Asociado a Receptor de TNF/metabolismo , Factor 6 Asociado a Receptor de TNF/genética , Osteoclastos/metabolismo , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Femenino , Fosfatidilinositol 3-Quinasas/metabolismo , Ratas , Ratones , Células RAW 264.7 , Flavonoides/farmacología , Osteogénesis/efectos de los fármacos , Ratas Sprague-Dawley , Osteoporosis/metabolismo , Osteoporosis/etiología , Ovariectomía/efectos adversos , Regulación de la Expresión Génica/efectos de los fármacos , Densidad Ósea/efectos de los fármacos
3.
Int J Cosmet Sci ; 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39119798

RESUMEN

OBJECTIVE: The objective is to develop a natural and stable anti-oxidative stress and anti-ageing ingredient. In this study, we evaluated the changes in white tea leaves fermented with Eurotium cristatum PLT-PE and Saccharomyces boulardii PLT-HZ and their efficacy against skin oxidative stress. METHODS: We employed untargeted metabolomics technology to analyse the differential metabolites between tea extract (TE) and fermented tea extract (FTE). In vitro, using H2O2-induced HaCaT cells, we evaluated cell vitality, ROS, and inflammatory factors (TNF-α, IL-1ß, and IL-6). Additionally, we verified the effects on the extracellular matrix and nuclear DNA using fibroblasts or reconstructed skin models. We measured skin hydration, elasticity, wrinkle area, wrinkle area ratio, erythema area, and erythema area ratio in volunteers after using an emulsion containing 3% FTE for 28 and 56 days. RESULTS: Targeted metabolomics analysis of white tea leaves yielded more than 20 differential metabolites with antioxidant and anti-inflammatory activities, including amino acids, polypeptides, quercetin, and liquiritin post-fermentation. FTE, compared to TE, can significantly reduce reactive oxygen species (ROS) and protect against oxidative stress-induced skin damage in H2O2-induced HaCaT cells. FTE can inhibit H2O2-induced collagen degradation by suppressing the MAPK/c-Jun signalling pathway and can also mitigate the reactive oxygen species damage to nuclear DNA. Clinical studies showed that the volunteers' stratum corneum water content, skin elasticity, wrinkle area, wrinkle area ratio, erythema area, and erythema area ratio significantly improved from the baseline after 28 and 56 days of FTE use. CONCLUSION: This study contributes to the growing body of literature supporting the protective effects against skin oxidative stress and ageing from fermented plant extracts. Moreover, our findings might inspire multidisciplinary efforts to investigate new fermentation techniques that could produce even more potent anti-ageing solutions.


OBJECTIF: L'objectif est de développer un ingrédient naturel et stable contre le stress oxydatif et anti­âge. Dans cette étude, nous avons évalué les modifications dans les feuilles de thé blanc fermentées avec la PLT­PE Eurotium cristatum et la PLT­HZ Saccharomyces boulardii et leur efficacité contre le stress oxydatif cutané. MÉTHODES: Nous avons utilisé une technologie de métabolomique non ciblée pour analyser les métabolites différentiels entre l'extrait de thé (ET) et l'extrait de thé fermenté (ETF). In vitro, à l'aide de cellules HaCaT induites par l'H2O2, nous avons évalué la vitalité cellulaire, les ERO et les facteurs inflammatoires (TNF­α, IL­1ß, and IL­6). Nous avons également vérifié les effets sur la matrice extracellulaire et l'ADN nucléaire à l'aide de fibroblastes ou de modèles cutanés reconstruits. Nous avons mesuré l'hydratation de la peau, l'élasticité, la surface de rides, le rapport des surfaces de rides, la surface d'érythème, et le rapport des surfaces d'érythème chez des volontaires ayant utilisé une émulsion contenant 3% d'ETF pendant 28 et 56 jours. RÉSULTATS: L'analyse métabolomique ciblée des feuilles de thé blanc a révélé plus de 20 métabolites différentiels ayant des activités antioxydantes et anti­inflammatoires, notamment des acides aminés, des polypeptides, de la quercétine et de la liquiritine après fermentation. Par rapport à l'ET, l'ETF peut réduire significativement les espèces réactives de l'oxygène (ERO) et protéger contre les lésions cutanées induites par le stress oxydatif dans les cellules HaCaT induites par l'H2O2. L'ETF peut inhiber la dégradation du collagène induite par l'H2O2 en supprimant la voie de signalization MAPK/c­Jun et peut également atténuer les dommages causés par les espèces réactives de l'oxygène à l'ADN nucléaire. Les études cliniques ont montré que la teneur en eau de la couche cornée des volontaires, l'élasticité de la peau, la surface de rides, le rapport des surfaces de rides, la surface d'érythème et le rapport des surfaces d'érythème se sont significativement améliorés par rapport à la référence après 28 et 56 jours d'utilisation d'ETF. CONCLUSION: Cette étude contribue au corpus croissant de littérature soutenant les effets protecteurs des extraits de plantes fermentées contre le stress oxydatif cutané et le vieillissement. En outre, nos résultats pourraient inspirer des efforts pluridisciplinaires pour étudier de nouvelles techniques de fermentation susceptibles de produire des solutions anti­âge encore plus puissantes.

5.
JBJS Case Connect ; 14(3)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39146447

RESUMEN

CASE: We present a unique case of a 45-year-old man with his right middle finger embedded with rings. Limited finger flexion was noted because of flexor tendon injury caused by the dorsal migration of the embedded ring through joint. The rings were removed under anesthesia, resulting in the resolution of swelling and recover of osseous structure. Follow-up examinations revealed no residual edema or numbness, indicating preserved neurovascularization, despite the dorsal migration of the ring. CONCLUSION: Our unique case reveals continuous finger ring migration without compromising neurovascular bundles, with review of 30 cases emphasizing the importance of psychiatric consultation. Timely intervention yielded nearly half of patients achieving full recovery.


Asunto(s)
Articulaciones de los Dedos , Humanos , Masculino , Persona de Mediana Edad , Traumatismos de los Dedos/cirugía , Migración de Cuerpo Extraño/diagnóstico por imagen
6.
Nat Commun ; 15(1): 6556, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39095386

RESUMEN

The migratory insertion of metal-hydride into alkene has allowed regioselective access to organometallics, readily participating in subsequent functionalization as one conventional pathway of hydroalkylation, whereas analogous process with feedstock alkyne is drastically less explored. Among few examples, the regioselectivity of metal-hydride insertion is mostly governed by electronic bias of alkynes. To alter the regioselectivity and drastically expand the intermediate pools that we can access, one aspirational design is through alternative nickel-alkyl insertion, providing opposite regioselectivity induced by steric demand. Leveraging in situ formed nickel-alkyl species, we herein report the regio- and enantioselective hydroalkylation of alkynes with broad functional group tolerance, excellent regio- and enantioselectivity, enabling efficient route to diverse valuable chiral allylic amines motifs. Preliminary mechanistic studies indicate the aminoalkyl radical species can participate in metal-capture and lead to formation of nickel-alkyl, of which the migratory insertion is key to reverse regioselectivity observed in metal-hydride insertion.

7.
Complement Ther Clin Pract ; 57: 101892, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39126817

RESUMEN

OBJECTIVES: This study aimed to explore the synergistic impact of online yoga, mindfulness practices, and probiotics on irritable bowel syndrome (IBS) by evaluating changes in physical fitness, mental health, and gut microbiota composition. DESIGN, SETTING AND INTERVENTIONS: The six-week randomized, double-blinded, placebo-controlled trial included 31 IBS patients categorized into three groups: online yoga with probiotics (EP), online yoga with a placebo (EC), and probiotics only (P). Assessments involved physical fitness tests, subjective questionnaires (IBS-QOL, BSRS-5), and gut microbiome analysis. MAIN OUTCOME MEASURES: Participants self-collected stool samples and were given a set of questionnaires at baseline and after six weeks of intervention. Their symptoms were measured by changes in the gut microbiota, physical fitness and quality of life, and psychological well-being. RESULTS: The EP group demonstrated improved cardiovascular endurance (P < 0.001) and a significant reduction in Klebsiella bacterial strains (P < 0.05). Both the EP and EC groups exhibited significantly decreased IBS-QOL scores (P < 0.001 and P < 0.05, respectively), indicating enhanced quality of life. While BSRS-5 scores decreased in both groups, the reduction was statistically insignificant. CONCLUSION: Integrating online yoga, mindfulness practices, and probiotics demonstrated comprehensive benefits for IBS patients. This intervention improved physical fitness and mental well-being and positively influenced gut microbiota composition. The study highlights the potential of this multifaceted approach in managing IBS symptoms and enhancing overall health, emphasizing the relevance of the gut-muscle-brain axis in understanding and addressing IBS complexities. TRIAL REGISTRATION: Taiwanese Registry of Institutional Review Board IRBHP210009/CH11000259.

8.
Small ; : e2402567, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39132749

RESUMEN

The photosynaptic transistor stands as a promising contender for overcoming the von Neumann bottleneck in the realm of photo-communication. In this context, photonic synaptic transistors is developed through a straightforward solution process, employing an organic semiconducting polymer with pendant-naphthalene-containing side chains (PDPPNA) in combination with ligand-density-engineered CsPbBr3 perovskite quantum dots (PQDs). This fabrication approach allows the devices to emulate fundamental synaptic behaviors, encompassing excitatory postsynaptic current, paired-pulse facilitation, the transition from short-to-long-term memory, and the concept of "learning experience." Notably, the phototransistor, incorporating the blend of the PDPPNA and CsPbBr3 PQDs washed with ethyl acetate, achieved an exceptional memory ratio of 104. Simultaneously, the same device exhibited an impressive paired-pulse facilitation ratio of 223% at a moderate operating voltage of -4 V and an extraordinarily low energy consumption of 0.215 aJ at an ultralow operating voltage of -0.1 mV. Consequently, these low-voltage synaptic devices, constructed with a pendant side-chain engineering of organic semiconductors and a ligand density engineering of PQDs through a simple fabrication process, exhibit substantial potential for replicating the visual memory capabilities of the human brain.

9.
World J Gastrointest Surg ; 16(7): 2362-2364, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39087113

RESUMEN

Laparoscopic colectomy with ileorectal anastomosis may be beneficial for patients with slow transit constipation who do not respond to conservative treatment, particularly if the superior rectal artery (SRA) is preserved. Several important concerns have been addressed in this commentary. It is important to first go over the definition of surgical procedure as it is used in this text. Second, the current study lacked a control group that had SRA preservation. Thirdly, it would be best to use a prospective, randomized controlled study. Lastly, a description of the mesenteric defect's state following a laparoscopic colectomy is necessary.

10.
Adv Sci (Weinh) ; : e2403578, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38973336

RESUMEN

Addressing the critical need for swift and precise nutritional profiling in healthcare and in food industry, this study pioneers the integration of vision-language models (VLMs) with chemical analysis techniques. A cutting-edge VLM is unveiled, utilizing the expansive UMDFood-90k database, to significantly improve the speed and accuracy of nutrient estimation processes. Demonstrating a macro-AUCROC of 0.921 for lipid quantification, the model exhibits less than 10% variance compared to traditional chemical analyses for over 82% of the analyzed food items. This innovative approach not only accelerates nutritional screening by 36.9% when tested amongst students but also sets a new benchmark in the precision of nutritional data compilation. This research marks a substantial leap forward in food science, employing a blend of advanced computational models and chemical validation to offer a rapid, high-throughput solution for nutritional analysis.

11.
Adv Sci (Weinh) ; : e2402284, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38994917

RESUMEN

Although messenger RNA translation is tightly regulated to preserve protein synthesis and cellular homeostasis, chronic exposure to interferon-γ (IFN-γ) in several cancers can lead to tryptophan (Trp) shortage via the indoleamine-2,3-dioxygenase (IDO)- kynurenine pathway and therefore promotes the production of aberrant peptides by ribosomal frameshifting and tryptophan-to-phenylalanine (W>F) codon reassignment events (substitutants) specifically at Trp codons. However, the effect of Trp depletion on the generation of aberrant peptides by ribosomal mistranslation in gastric cancer (GC) is still obscure. Here, it is shows that the abundant infiltrating lymphocytes in EBV-positive GC continuously secreted IFN-γ, upregulated IDO1 expression, leading to Trp shortage and the induction of W>F substitutants. Intriguingly, the production of W>F substitutants in EBV-positive GC is linked to antigen presentation and the activation of the mTOR/eIF4E signaling pathway. Inhibiting either the mTOR/eIF4E pathway or EIF4E expression counteracted the production and antigen presentation of W>F substitutants. Thus, the mTOR/eIF4E pathway exposed the vulnerability of gastric cancer by accelerating the production of aberrant peptides and boosting immune activation through W>F substitutant events. This work proposes that EBV-positive GC patients with mTOR/eIF4E hyperactivation may benefit from anti-tumor immunotherapy.

12.
Curr Med Sci ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38990449

RESUMEN

OBJECTIVE: This study aimed to investigate the role of the long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) in the epithelial-mesenchymal transition (EMT) of bladder cancer cells and the potential mechanisms. METHODS: Cell invasion, migration, and wound healing assays were conducted to assess the effects of MEG3 on the invasive and migratory capabilities of bladder cancer cells. The expression levels of E-cadherin were measured using Western blotting, RT-qPCR, and dual luciferase reporter assays. RNA immunoprecipitation and pull-down assays were performed to investigate the interactions between MEG3 and its downstream targets. RESULTS: MEG3 suppressed the invasion and migration of bladder cancer cells and modulated the transcription of E-cadherin. The binding of MEG3 to the zinc finger region of the transcription factor Snail prevented its ability to transcriptionally repress E-cadherin. Additionally, MEG3 suppressed the phosphorylation of extracellular regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), and P38, thereby decreasing the expression of Snail and stimulating the expression of E-cadherin. CONCLUSION: MEG3 plays a vital role in suppressing the EMT in bladder cancer cells, indicating its potential as a promising therapeutic target for the treatment of bladder cancer.

13.
J Chin Med Assoc ; 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39017646

RESUMEN

BACKGROUND: The associations of COVID-19 with Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) remain unclear. Few large-scale studies have estimated the cumulative incidence of MIS-C and KD after COVID-19 in children. METHODS: Data were obtained from TriNetX. After propensity score matching was completed, data from 258,645 patients with COVID-19 (COVID-19 group) and 258,645 patients without COVID-19 (non-COVID-19 group) were analyzed using Cox regression. Hazard ratio (HR), 95% confidence interval (CI), and cumulative incidence of MIS-C and KD were calculated for both groups. Stratified analysis was performed to validate the results. RESULTS: After matching for age at baseline and sex, the risks of MIS-C and KD were higher in the COVID-19 group than in the non-COVID-19 group (HR: 3.023 [95% CI: 2.323 to 3.933] and 1.736 [95% CI: 1.273 to 2.369], respectively). After matching for age at baseline, sex, race, ethnicity, and comorbidities, the risks of MIS-C and KD remained significantly higher in the COVID-19 group than in the non-COVID-19group (HR: 2.899 [95% CI: 2.173 to 3.868] and 1.435 [95% CI: 1.030 to 2.000]). When stratified by age, the risk of MIS-C was higher in the COVID-19 group-for patients aged > 5 years and ≤ 5 years (HR: 2.399 [95% CI: 1.683 to 3.418] and 2.673 [95% CI: 1.737 to 4.112], respectively)-than in the non-COVID-19 group. However, the risk of KD was elevated only in patients aged ≤ 5 years (HR: 1.808; 95% CI: 1.203 to 2.716). When stratified by COVID-19 vaccination status, the risks of MIS-C and KD were elevated in unvaccinated patients with COVID-19 (HR: 2.406 and 1.835, respectively). CONCLUSION: Patients with COVID-19 who are aged < 18 and ≤ 5 years have increased risks of MIS-C and KD, respectively. Further studies are required to confirm the role of COVID-19 in the pathogenesis of MIS-C and KD.

14.
Artículo en Inglés | MEDLINE | ID: mdl-39010712

RESUMEN

PURPOSE: To compare side-to-side superior capsular reconstruction (SCR) with over-the-top SCR in terms of functional outcomes, pain relief and allograft survival rates. METHODS: Patients who had undergone arthroscopic dermal allograft SCR for massive irreparable rotator cuff tears and clinical follow-up for ≥2 years were recruited. All patients underwent postoperative assessment with routine radiographic analysis for acromiohumeral distances, ultrasound imaging 1 and 3 months after SCR and magnetic resonance imaging (MRI) at least 12 months after SCR. The outcome measures were visual analogue scale (VAS), American Shoulder and Elbow Surgeons (ASES), Constant and Single Assessment Numeric Evaluation (SANE) scores. RESULTS: SCR was performed in 56 patients including side-to-side SCR in 32 and over-the-top SCR in 24. Postoperative MRI showed that the grafts were intact in 46 patients (82.1%; 26 who underwent side-to-side SCR and 20 who underwent over-the-top SCR). The proportion of nonhealing grafts in the over-the-top group was significantly higher with concomitant subscapularis tears (60% vs. 5.3%; p = 0.02). VAS scores and functional outcomes improved postoperatively in both groups and postoperative VAS (1.4 vs. 1.7; n.s.), Constant (74.8 vs. 76.0; n.s.), mean ASES (87.4 vs. 89.1; n.s.) and mean SANE (81.7 vs. 84.3; n.s.) scores did not differ significantly. CONCLUSION: For massive rotator cuff tears, over-the-top and side-to-side SCR achieve similar pain relief and functional improvement, and the rate of healing allografts is high. However, over-the-top SCR is not recommended for massive posterosuperior rotator cuff tears with repairable subscapularis tendon tears due to a higher nonhealing rate. LEVEL OF EVIDENCE: Level III.

16.
Artículo en Inglés | MEDLINE | ID: mdl-39034165

RESUMEN

BACKGROUND: The adverse effects of sepsis-associated acute kidney injury (SA-AKI) highlight the need for new biomarkers. Signal Peptide-Complement C1r/C1s, Uegf, Bmp1-Epidermal Growth Factor-like Domain-Containing Protein 2 (SCUBE2), important for angiogenesis and endothelial integrity, has been linked to increased mortality in models of lipopolysaccharide-induced lung injury. This research aimed to assess the utility of plasma SCUBE2 levels as a prognostic indicator for SA-AKI in intensive care unit (ICU) patients. METHODS: Between September 2020 and December 2022, our study enrolled ICU patients diagnosed with stage 3 SA-AKI. We collected demographic information, illness severity indices, and laboratory data, including plasma SCUBE2 and sepsis-triggered cytokine levels. We employed receiver operating characteristic curves and DeLong tests to assess the predictive accuracy for survival, Kaplan-Meier curves to evaluate the relative risk of death, and multivariate logistic regression to identify independent mortality predictors. RESULTS: Among the total of 200 participants, the survivors had significantly higher plasma SCUBE2 levels (115.9 ng/mL) compared to those who died (35.6 ng/mL). SCUBE2 levels showed a positive correlation with the anti-inflammatory cytokine IL-10 and a negative correlation with the APACHE II score, SOFA score, C-reactive protein, and monocyte chemoattractant protein-1. Multivariate analysis revealed that elevated SCUBE2 and IL-10 levels were independently protective against mortality, and associated with the most favorable 30-day survival outcomes. CONCLUSIONS: In ICU patients with stage 3 SA-AKI, lower plasma levels of SCUBE2 were correlated with elevated pro-inflammatory factors, which impacted survival outcomes. This suggests that SCUBE2 could be a potential biomarker for predicting prognosis in patients with SA-AKI.

18.
Cell Chem Biol ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-39025070

RESUMEN

Morphinan antagonists, which block opioid effects at mu-opioid receptors, have been studied for their analgesic potential. Previous studies have suggested that these antagonists elicit analgesia with fewer adverse effects in the presence of the mutant mu-opioid receptor (MOR; S196A). However, introducing a mutant receptor for medical applications represents significant challenges. We hypothesize that binding a chemical compound to the MOR may elicit a comparable effect to the S196A mutation. Through high-throughput screening and structure-activity relationship studies, we identified a modulator, 4-(2-(4-fluorophenyl)-4-oxothiazolidin-3-yl)-3-methylbenzoic acid (BPRMU191), which confers agonistic properties to small-molecule morphinan antagonists, which induce G protein-dependent MOR activation. Co-application of BPRMU191 and morphinan antagonists resulted in MOR-dependent analgesia with diminished side effects, including gastrointestinal dysfunction, antinociceptive tolerance, and physical and psychological dependence. Combining BPRMU191 and morphinan antagonists could serve as a potential therapeutic strategy for severe pain with reduced adverse effects and provide an avenue for studying G protein-coupled receptor modulation.

19.
Micromachines (Basel) ; 15(7)2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-39064388

RESUMEN

This paper presents a new framework using MEMS flow sensors on turbine blades (SOTB) to investigate unsteady flow features of a rotating wind turbine. Self-heating flow sensors were implemented by the U18 complementary metal-oxide semiconductor (CMOS) MEMS foundry provided by Taiwan Semiconductor Research Institute (TSRI). Flow sensor chips with a size of 1.5 mm × 1.5 mm were parylene-coated, output via a wireless data acquisition system (WDAQ), and mounted at the root, middle and tip of a 1.2 m diameter semi-rigid turbine blade of a 400 W horizontal axis wind turbine (HAWT). The instantaneous angles of attack (AOAs) of the SOTB were found to be 46~62°, much higher than the general stall AOA of 15°, but were accurate considering the normal detection of the flow sensors. The computational fluid dynamics (CFD) simulation of the HAWT was also compared with the SOTB output. The onsite measurement herein revealed that the 3D secondary flow increment, mostly obvious near the middle part of the turbine blades, degraded both the sensor and the turbine performance and initially justified the onsite measurement application.

20.
J Infect Public Health ; 17(8): 102495, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39018725

RESUMEN

BACKGROUND: Chronic fatigue syndrome (CFS) has been linked to several conditions, including infections, immune system changes, or emotional stress. Our study aimed to assess the risk of CFS after a pneumonia diagnosis using data from National Health Insurance Research Database of Taiwan. METHODS: In this nested case-control study, we identified 2,000,000 adult patients from a nationwide population-based health insurance claims database spanning from January 1, 2000, to December 31, 2017. Each case diagnosed with a pathogenic infection was matched with a corresponding control using propensity scores. We excluded individuals under 20 years of age, those with a history of pathogenic infections before the index date, or those with more than one potential pathogen. To estimate hazard ratios (HR) and the adjusted hazard ratio (aHR) with their respective 95 % confidence intervals (CI), we applied univariable and multivariable Cox proportional hazard models. The multivariable analysis incorporated adjustments for age, sex, and comorbidity-related confounders. RESULTS: The relationship between infection and the subsequent risk of CFS was assessed using Cox proportional hazards regression analysis. The incidence density rates were 6.13 and 8.70 per 1000 person-years among the non-pulmonary infection and pulmonary infection populations, respectively (adjusted hazard ratio [HR] = 1.4, 95 % confidence interval [CI] 1.32-1.5). Patients infected with Pseudomonas, Klebsiella pneumoniae, Haemophilus influenzae, Streptococcus pneumoniae, and influenza virus exhibited a significantly higher risk of CFS than those without these pathogens (p < 0.05). Additionally, patients with pneumonia had a significantly increased risk of thromboembolism compare with control group (p < 0.05).


Asunto(s)
Síndrome de Fatiga Crónica , Neumonía , Modelos de Riesgos Proporcionales , Humanos , Síndrome de Fatiga Crónica/epidemiología , Masculino , Femenino , Taiwán/epidemiología , Estudios de Casos y Controles , Adulto , Persona de Mediana Edad , Neumonía/epidemiología , Neumonía/etiología , Incidencia , Factores de Riesgo , Anciano , Adulto Joven , Estudios de Cohortes , Bases de Datos Factuales
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