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A series of trans-RuL(PPh3)2(nitrile) and {RuL(PPh3)2}.2-µ-(nitrile)-based complexes [where L = 2,2'-(3,4-diphenyl-pyrrole-2,5-diyl)dipyridine (dpp), di(pyridin-2-yl)isoindoline-1,3-diimine (bpi), or 4-(4-methoxyphenyl)-6-phenyl-2,2'-bipyridine (Pbpy); and nitrile = 1,4-dibenzontirile, 4-ethynylbenzonitrile, or dicyanamide] were synthesized and characterized, and their electrochemical and photochemical behaviors were investigated. Those complexes that contained a significant nitrile contribution to their 3MLLCT show a release of their nitrile ligand (when L = dpp or Pbpy and the nitrile ligand = 4-dibenzontirile, or 4-ethynylbenzonitrile) with dissociation constants up to 8.09 × 10-4 s-1.
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Bacterial genotoxins damage host cells by targeting their chromosomal DNA. In the present study, we demonstrate that a genotoxin of Salmonella Typhi, typhoid toxin, triggers the senescence-associated secretory phenotype (SASP) by damaging mitochondrial DNA. The actions of typhoid toxin disrupt mitochondrial DNA integrity, leading to mitochondrial dysfunction and disturbance of redox homeostasis. Consequently, it facilitates the release of damaged mitochondrial DNA into the cytosol, activating type I interferon via the cGAS-STING pathway. We also reveal that the GCN2-mediated integrated stress response plays a role in the upregulation of inflammatory components depending on the STING signaling axis. These SASP factors can propagate the senescence effect on T cells, leading to senescence in these cells. These findings provide insights into how a bacterial genotoxin targets mitochondria to trigger a proinflammatory SASP, highlighting a potential therapeutic target for an anti-toxin intervention.
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Fenotipo Secretor Asociado a la Senescencia , Fiebre Tifoidea , Humanos , Fiebre Tifoidea/metabolismo , Mutágenos/metabolismo , Senescencia Celular/fisiología , Mitocondrias/metabolismo , ADN Mitocondrial/metabolismo , Salmonella , FenotipoRESUMEN
This study entailed a comprehensive GCâMS analysis conducted on 121 patient samples to generate a clinical breathomics dataset. Breath molecules, indicative of diverse conditions such as psychological and pathological states and the microbiome, were of particular interest due to their non-invasive nature. The highlighted noninvasive approach for detecting these breath molecules significantly enhances diagnostic and monitoring capacities. This dataset cataloged volatile organic compounds (VOCs) from the breath of individuals with asthma, bronchiectasis, and chronic obstructive pulmonary disease. Uniform and consistent sample collection protocols were strictly adhered to during the accumulation of this extensive dataset, ensuring its reliability. It encapsulates extensive human clinical breath molecule data pertinent to three specific diseases. This consequential clinical breathomics dataset is a crucial resource for researchers and clinicians in identifying and exploring important compounds within the patient's breath, thereby augmenting future diagnostic and therapeutic initiatives.
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Asma , Pruebas Respiratorias , Bronquiectasia , Enfermedad Pulmonar Obstructiva Crónica , Compuestos Orgánicos Volátiles , Humanos , Asma/diagnóstico , Pruebas Respiratorias/métodos , Espiración , Reproducibilidad de los Resultados , Compuestos Orgánicos Volátiles/análisis , Cromatografía de Gases y Espectrometría de Masas , Bronquiectasia/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/diagnósticoRESUMEN
This study estimates the association between sarcopenia and blood biochemical parameters, nutritional intake, anthropometric measurements, physical performance, and physical activity in patients with type 2 diabetes mellitus (T2DM). Participants were recruited from a primary care clinic in Kaohsiung City. According to the diagnosis criteria of the Asian Working Group for Sarcopenia (AWGS) in 2019, 110 patients with T2DM (aged 50-80 years) were divided into three groups: non-sarcopenia (n = 38), possible sarcopenia (n = 31), and sarcopenia (n = 41). Blood samples were collected, and nutritional intake was evaluated by a registered dietitian. A food frequency questionnaire and a Godin leisure-time exercise questionnaire were used to assess their daily vitamin D intake and physical activity. There were significant differences in age, serum vitamin D levels, nutritional intake, anthropometric measurements, and physical performance between the three groups. In elderly patients with T2DM, reduced serum 25-hydroxyvitamin D [25(OH)D] levels and daily energy intake were significantly associated with possible sarcopenia. Age, lower BMI, reduced serum 25(OH)D, and reduced dietary protein and vitamin D intake were significantly associated with sarcopenia. These findings may serve as the basis for intervention trials to reduce the prevalence of sarcopenia.
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Diabetes Mellitus Tipo 2 , Sarcopenia , Anciano , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Taiwán/epidemiología , Sarcopenia/epidemiología , Sarcopenia/etiología , Composición Corporal , Ingestión de Alimentos , Ejercicio Físico , Vitamina DRESUMEN
Introduction: There are differences in the gut microbiome and metabolome when the host undergoes different physical or pathological conditions. However, the inter-relationship of microbiome and metabolome biomarkers to potentially promote the health of dairy cows needs to be studied. Further, the development of next-generation probiotics for dairy cattle health promotion has not been demonstrated. Objective: In the present study, we identified the microbiome and metabolome biomarkers associated with healthy cows. Methods: We analyzed the relationships of the ruminal microorganism profile and metabolites between healthy and mastitis lactating dairy cows. The roles of bacterial biomarker were further verified by in vitro fermentation and cow-to-mouse fecal microbiota transplantation (FMT). Results: Two species, Ruminococcus flavefaciens and Bifidobacterium longum subsp. longum, and six rumen metabolites were positively correlated with healthy cows by Spearman's correlation analysis. Through in vitro ruminal fermentation, inoculating R. flavefaciens and B. longum subsp. longum showed the upregulation of the levels of putrescine, xanthurenic acid, and pyridoxal in the mastitis ruminal fluid, which confirmed the inter-relationships between these microbiota and metabolites associated with healthy cows. Further, we verified the role of R. flavefaciens and B. longum subsp. longum in promoting health by FMT. The administration of R. flavefaciens and B. longum subsp. longum reduced the death rate and recovered the bodyweight loss of germ-free mice caused by FMT mastitis feces. Discussion: We provided evidence that the bacterial biomarkers alter downstream metabolites. This could indirectly indicate that the two bacterial biomarkers have the potential to be used as next-generation probiotics for dairy cattle, although it needs more evidence to support our hypothesis. Two species, R. flavefaciens and B. longum subsp. longum, with three metabolites, putrescine, xanthurenic acid, and pyridoxal, identified in the ruminal fluid, may point to a new health-promoting and disease-preventing approach for dairy cattle.
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Visual working memory possesses capacity constraints limiting the availability of resources for encoding and maintaining information. Studies have shown that prospective rewards improve performance on visual working memory tasks, but it remains unclear whether rewards increase total resource availability or simply influence the allocation of resources. Participants performed a continuous report visual working memory task with oriented grating stimuli. On each trial, participants were presented with a priority cue, which signaled the item most likely to be probed, and a reward cue, which signaled the magnitude of a performance-contingent reward. We showed that rewards decreased recall error for cued items and increased recall error for noncued items. This tradeoff was due to a change in the probability of successfully encoding a cued versus a noncued item rather than a change in recall precision or the probability of binding errors. Rewards did not modulate performance when priority cues were retroactively presented after the stimulus presentation period, indicating that rewards only affect resource allocation when participants are able to engage proactive control before encoding. Additionally, reward had no effect on visual working memory performance when priority cues were absent and thus unable to guide resource allocation. These findings indicate that rewards influence the flexible allocation of resources during selection and encoding in visual working memory, but do not augment total capacity. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Señales (Psicología) , Memoria a Corto Plazo , Humanos , Estudios Prospectivos , Recuerdo Mental , Recompensa , Percepción VisualRESUMEN
Emissive compounds with long emission lifetimes (µs to ms) in the visible region are of interest for a range of applications, from oxygen sensing to cellular imaging. The emission behavior of Ir(ppy)2(acac) complexes (where ppy is the 2-phenylpyridyl chelate and acac is the acetylacetonate chelate) with an oligo(para-phenyleneethynylene) (OPE3) motif containing three para-rings and two ethynyl bridges attached to acac or ppy is examined here due to the accessibility of the long-lived OPE3 triplet states. Nine Ir(ppy)2(acac) complexes with OPE3 units are synthesized where the OPE3 motif is at the acac moiety (aOPE3), incorporated in the ppy chelate (pOPE3) or attached to ppy via a durylene link (dOPE3). The aOPE3 and dOPE3 complexes contain OPE3 units that are decoupled from the Ir(ppy)2(acac) core by adopting perpendicular ring-ring orientations, whereas the pOPE3 complexes have OPE3 integrated into the ppy ligand to maximize electronic coupling with the Ir(ppy)2(acac) core. While the conjugated pOPE3 complexes show emission lifetimes of 0.69-32.8 µs similar to the lifetimes of 1.00-23.1 µs for the non-OPE3 Ir(ppy)2(acac) complexes synthesized here, the decoupled aOPE3 and dOPE3 complexes reveal long emission lifetimes of 50-625 µs. The long lifetimes found in aOPE3 and dOPE3 complexes are due to intramolecular reversible electronic energy transfer (REET) where the long-lived triplet-state metal to ligand charge transfer (3MLCT) states exchange via REET with the even longer-lived triplet-state localized OPE3 states. The proposed REET process is supported by changes observed in excitation wavelength-dependent and time-dependent emission spectra from aOPE3 and dOPE3 complexes, whereas emission spectra from pOPE3 complexes remain independent of the excitation wavelength and time due to the well-established 3MLCT states of many Ir(ppy)2(acac) complexes. The long lifetimes, visible emission maxima (524-526 nm), and photoluminescent quantum yields of 0.44-0.60 for the dOPE3 complexes indicate the possibility of utilizing such compounds in oxygen-sensing and cellular imaging applications.
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Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complicated inflammatory disease, and the underlying mechanism remains unclear. While some reactive oxygen/nitrogen species-related gene products are reported to participate in CRSwNP, a systemic and full analysis of oxidative-stress-associated genes in CRSwNP has not been extensively studied. Therefore, this study sought to catalog the gene-expression patterns related to oxidative stress and antioxidant defense in control and CRSwNP patients. In total, 25 control and 25 CRSwNP patients were recruited. The distribution and expression of 4-hydroxynonenal and 3-nitrotyrosine as markers of oxidative stress-which is represented by lipid peroxidation and the protein nitration of tyrosine residues in CRSwNP nasal polyps (NPs)-were more apparently increased than those found in the control nasal mucosae, as determined by immunohistochemistry (IHC). The expression of 84 oxidative-stress-related genes in nasal mucosae and NP tissues was analyzed via real-time PCR, which showed that 19 genes and 4 genes were significantly up- and downregulated, respectively; among them, inducible nitric oxide synthase (iNOS) and heme oxygenase 1 (HO-1) were notably upregulated, whereas lactoperoxidase (LPO), myeloperoxidase (MPO), and superoxide dismutase 3 (SOD3) were highly downregulated. Changes in the mRNA and protein levels of these redox proteins were confirmed with a customized, real-time PCR array and RT-PCR analysis, as well as Western blotting and IHC assays. A receiver operating characteristic curve analysis further suggested that LPO, MPO, SOD3, HO-1, and iNOS are possible endotype predictors of CRSwNP development. Collectively, we present an oxidative-stress-related gene profile of CRSwNP NP tissues, providing evidence that the systemic changes in oxidative stress and the antioxidative defense system, including novel iNOS, heme peroxidases, and other genes, are closely linked to CRSwNP pathology, development, and progression.
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Bis-heteroleptic cyclometalated iridium complexes of the form Ir(La)2(acac), where La is a substituted 2-phenylpyridine derivative and acac is an acetylacetonato ligand, are a useful class of luminescent organometallic complexes for a range of applications. Related tris-heteroleptic complexes of the form Ir(La)(Lb)(acac) offer the potential advantage of greater functionality through the use of two different cyclometalated ligands but are, in general, more difficult to obtain. We report the synthesis of divergent bis- and tris-heteroleptic triisopropylsilylethynyl-substituted intermediate complexes that can be diversified using a "chemistry-on-the-complex" approach. We demonstrate the methodology through one-pot deprotection and Sonogashira cross-coupling of the intermediate complexes with para-R-aryliodides (R = H, SMe, and CN). The photophysical and electrochemical behaviors of the resultant bis- and tris-heteroleptic complexes are compared, and it is shown that the tris-heteroleptic complexes exhibit subtly different emission and redox properties to the bis-heteroleptic complexes, such as further red-shifted emission maxima and lower extinction coefficients, which can be attributed to the reduced symmetry. It is demonstrated, supported by DFT and time-dependent DFT calculations, that the charge-transfer character of the emission can be altered via variation of the terminal substituent; the introduction of an electron-withdrawing cyano group in the terminal position leads to a significant red shift, while the introduction of an SMe group can substantially increase the emission quantum yield. Most notably, this convenient synthetic approach reduces the need to perform the often challenging isolation of tris-heteroleptic complexes to a single divergent intermediate, which will simplify access to families of complexes of the form Ir(La)(Lb)(acac).
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BACKGROUND: Pectus excavatum (PE) negatively impacts psychological function, but its effect on autonomic nervous system (ANS) function has not been investigated. We evaluated ANS function following postural changes in patients with PE. METHODS: The participants were 14 healthy men (control group) and 20 men with PE (study group). Psychological function was assessed using the visual analog scale for pain, Brief Symptom Rating Scale-5, and Beck Depression Inventory-II. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI). ANS regulation in response to postural change was measured in the supine position and immediately after sitting. All measurements were compared between the control and study groups at baseline and between the study groups before and after Nuss surgery. RESULTS: At baseline, upon postural change, symptomatic activity increased in the control group (50.3-67.4%, p = 0.035) but not in the study group (55.0-54.9%, p = 0.654); parasympathetic activity decreased in the control group (49.7-32.6%, p = 0.035) but not in the study group (45.1-45.1%, p = 0.654); and overall ANS regulation increased in the control group (1.02-2.08, p = 0.030) but not in the study group (1.22-1.22, p = 0.322). In response to postural change after Nuss surgery in the study group, sympathetic activity increased (48.7-70.2%, p = 0.005), parasympathetic activity decreased (51.3-29.8%, p = 0.005), and overall ANS regulation increased (0.95-2.36, p = 0.012). CONCLUSION: ANS function in response to postural change is dysregulated in patients with PE, which improved after Nuss surgery. Trial registration ClinicalTrials.gov, ID: NCT03346876, November 15, 2017, retrospectively registered, https://register. CLINICALTRIALS: gov/prs/app/action/SelectProtocol?sid=S0007KGI&selectaction=Edit&uid=U0003JZU&ts=2&cx=cstxeg.
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Tórax en Embudo , Sistema Nervioso Autónomo/fisiología , Femenino , Tórax en Embudo/cirugía , Humanos , Masculino , Proyectos Piloto , Taiwán , Escala Visual AnalógicaRESUMEN
Typhoid toxin is an essential virulence factor for Salmonella Typhi, the cause of typhoid fever in humans. This toxin has an unusual biology in that it is produced by Salmonella Typhi only when located within host cells. Once synthesized, the toxin is secreted to the lumen of the Salmonella-containing vacuole from where it is transported to the extracellular space by vesicle carrier intermediates. Here, we report the identification of the typhoid toxin sorting receptor and components of the cellular machinery that packages the toxin into vesicle carriers, and exports it to the extracellular space. We found that the cation-independent mannose-6-phosphate receptor serves as typhoid toxin sorting receptor and that the coat protein COPII and the GTPase Sar1 mediate its packaging into vesicle carriers. Formation of the typhoid toxin carriers requires the specific environment of the Salmonella Typhi-containing vacuole, which is determined by the activities of specific effectors of its type III protein secretion systems. We also found that Rab11B and its interacting protein Rip11 control the intracellular transport of the typhoid toxin carriers, and the SNARE proteins VAMP7, SNAP23, and Syntaxin 4 their fusion to the plasma membrane. Typhoid toxin's cooption of specific cellular machinery for its transport to the extracellular space illustrates the remarkable adaptation of an exotoxin to exert its function in the context of an intracellular pathogen.
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Inmunotoxinas , Fiebre Tifoidea , Humanos , Inmunotoxinas/metabolismo , Salmonella , Salmonella typhi/metabolismoRESUMEN
Being one of the renal replacement therapies, peritoneal dialysis (PD) maintains around 15% of end-stage kidney disease patients' lives; however, complications such as peritoneal fibrosis and ultrafiltration failure during long-term PD compromise its application. Previously, we established a sodium hypochlorite (NaClO)-induced peritoneal fibrosis porcine model, which helped to bridge the rodent model toward pre-clinical human peritoneal fibrosis research. In this study, the peritoneal equilibration test (PET) was established to evaluate instant functional changes in the peritoneum in the pig model. Similar to observations from long-term PD patients, increasing small solutes transport and loss of sodium sieving were observed. Mechanistic investigation from both in vivo and in vitro data suggested that disruption of cytoskeleton induced by excessive reactive oxygen species defected intracellular transport of aquaporin 1, this likely resulted in the disappearance of sodium sieving upon PET. Functional interference of aquaporin 1 on free water transport would result in PD failure in patients.
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A 75-year-old previously healthy female became severely ill, functionally dependent, and required long-term home oxygen therapy, after recovery from coronavirus disease 2019 (COVID-19) with acute respiratory failure and extensive pulmonary fibrosis. After two months of respiratory muscle training and a comprehensive cardiopulmonary rehabilitation program, her dyspnea, physical performance, pulmonary function parameters, and activities of daily living rapidly improved. This Case highlights the importance of a timely active rehabilitation program for COVID-19 survivors experiencing the long-term effects of coronavirus (long COVID).
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COVID-19 , Infecciones por Coronavirus , Coronavirus , Actividades Cotidianas , Anciano , COVID-19/complicaciones , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/terapia , Femenino , Humanos , Calidad de Vida , Síndrome Post Agudo de COVID-19RESUMEN
Severe acute respiratory syndrome-associated coronavirus 2 is a major global health issue and is driving the need for new therapeutics. The surface spike protein, which plays a central role in virus infection, is currently the target for vaccines and neutralizing treatments. The emergence of novel variants with multiple mutations in the spike protein may reduce the effectiveness of neutralizing antibodies by altering the binding activity of the protein with angiotensin-converting enzyme 2 (ACE2). To understand the impact of spike protein mutations on the binding interactions required for virus infection and the effectiveness of neutralizing monoclonal antibody (mAb) therapies, the binding activities of the original spike protein receptor binding domain (RBD) sequence and the reported spike protein variants were investigated using surface plasmon resonance. In addition, the interactions of the ACE2 receptor, an anti-spike mAb (mAb1), a neutralizing mAb (mAb2), the original spike RBD sequence, and mutants D614G, N501Y, N439K, Y453F, and E484K were assessed. Compared to the original RBD, the Y453F and N501Y mutants displayed a significant increase in ACE2 binding affinity, whereas D614G had a substantial reduction in binding affinity. All mAb-RBD mutant proteins displayed a reduction in binding affinities relative to the original RBD, except for the E484K-mAb1 interaction. The potential neutralizing capability of mAb1 and mAb2 was investigated. Accordingly, mAb1 failed to inhibit the ACE2-RBD interaction while mAb2 inhibited the ACE2-RBD interactions for all RBD mutants, except mutant E484K, which only displayed partial blocking.
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Severe acute respiratory syndrome-associated coronavirus 2 is a major global health issue and is driving the need for new therapeutics.The surface spike protein,which plays a central role in virus infection,is currently the target for vaccines and neutralizing treatments.The emergence of novel variants with multiple mutations in the spike protein may reduce the effectiveness of neutralizing antibodies by altering the binding activity of the protein with angiotensin-converting enzyme 2(ACE2).To understand the impact of spike protein mutations on the binding interactions required for virus infection and the effectiveness of neutralizing monoclonal antibody(mAb)therapies,the binding activities of the original spike protein receptor binding domain(RBD)sequence and the reported spike protein variants were investigated using surface plasmon resonance.In addition,the interactions of the ACE2 receptor,an anti-spike mAb(mAb1),a neutralizing mAb(mAb2),the original spike RBD sequence,and mutants D614G,N501Y,N439K,Y453F,and E484K were assessed.Compared to the original RBD,the Y453F and N501Y mutants displayed a significant increase in ACE2 binding affinity,whereas D614G had a substantial reduction in binding affinity.All mAb-RBD mutant proteins displayed a reduction in binding affinities relative to the original RBD,except for the E484K-mAb1 interaction.The potential neutralizing capability of mAb1 and mAb2 was investigated.Accordingly,mAb1 failed to inhibit the ACE2-RBD interaction while mAb2 inhibited the ACE2-RBD interactions for all RBD mutants,except mutant E484K,which only dis-played partial blocking.
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This study was to examine the airborne particulates/dusts and worker exposures in electro-static powder coating operations. Temporal variation and size distribution of dusts were assessed using direct-reading instrument, while the worker task-specific dust exposures (n = 41) were measured in three factories using conventional filter method. Additionally, toxic metal levels in the coating powder (n = 27) were analyzed to assess hazard potentials. Continuous monitoring of airborne respirable dust levels indicated large temporal variation across a normal working day. The particulate levels outside spraying booths were generally low (below 0.10 mg m-3) during normal spraying operation, but short-term level may reach as high as 21.8 mg m-3 (averaged at 4-5 mg m-3) when specific task such as cleaning the pipelines and spraying booth, was performed. Exploratory assessment on particle size distribution at four major working zones, administration, uploading, spraying, and baking, indicated no major difference among the zones, and between factories. The particle count median aerodynamic diameter was 0.88-1.69 µm, while the mean number concentrations were 10.97, 15.17, 18.49, and 27.03 (# cm-3) for zones administration, uploading, spraying, and baking, respectively. The worker task-specific dust exposures were found low during normal spraying, with the mean short-term total and respirable dust concentrations being 0.88 and 0.41 mg m-3, respectively. Both levels increased to 3.48 and 5.19 mg m-3, respectively (P < 0.05), if powder changing and system cleaning were done. Short-term total and respirable dust concentrations were 94.2 and 56.1 mg m-3, respectively, when complete cleaning process was performed inside spraying booth. Both levels exceeded the short-term exposure limits. The mean concentration of metals in the powder samples were 6.78, 9.52, 10 717, 2805, 1020, and 1361 µg g-1 for Pb, Cr (total), Al, Fe, Cu, and Sr, respectively. This study demonstrated that cleaning of spraying booth resulted in high dust exposures well exceeding the exposure limit. Toxic metals, particularly Pb, Cd, and Cr (total), levels measured in the powder samples were found low, and the resulting exposures were below the exposure limits, indicating relative low risks associated with the exposure at current dust levels.
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Contaminantes Ocupacionales del Aire , Exposición Profesional , Contaminantes Ocupacionales del Aire/análisis , Polvo/análisis , Monitoreo del Ambiente , Humanos , Exposición Profesional/análisis , Tamaño de la Partícula , Polvos , Valores Limites del UmbralRESUMEN
BACKGROUND: The purpose of this study was to determine the efficacy of a mandibular advancement device (MAD) for increasing patient safety during sedated total knee arthroplasty (TKA) and total hip replacement (THR). METHODS: Forty patients undergoing TKA or THR surgery in the supine or lateral recumbent positions under spinal anesthesia were enrolled. Sedation and oxygenation were administered. The MAD (Sweet Sleep Anti-Snoring Device) was then placed after 15 minutes of observation. SpO2, PetCO2, blood pressure, and respiratory rate were recorded. RESULTS: Sedated patients in the decubitus position had higher saturation nadirs, shorter desaturation durations, shorter airway obstruction durations, and fewer rescue events than those in the supine position. In patients at a high risk of obstructive sleep apnea syndrome (OSAS), desaturation duration, obstruction duration, apnea duration, desaturation duration, and rescue events were significantly lower after MAD placement. However, the saturation nadir did not improve after MAD placement. CONCLUSION: The MAD may shorten the duration of desaturation events during spontaneous breathing sedative procedures in the lateral recumbent position but not in the supine position. Breathing patterns did not change from nasal breathing to oral breathing or vice versa between pre- and postplacement of the MAD. Sedation score evaluation affects breathing pattern changes from oral breathing to nasal breathing and vice versa.
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Anestesia , Anestésicos Intravenosos/administración & dosificación , Ferulas Oclusales , Seguridad del Paciente , Propofol/administración & dosificación , Apnea Obstructiva del Sueño , Adulto , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Femenino , Humanos , Masculino , Persona de Mediana Edad , Saturación de Oxígeno , TaiwánRESUMEN
Patients with kidney failure rely on life-saving peritoneal dialysis to facilitate waste exchange and maintain homeostasis of physical conditions. However, peritoneal dialysis often results in peritoneal fibrosis and organ adhesion that subsequently compromise the efficiency of peritoneal dialysis and normal functions of visceral organs. Despite rodent models provide clues on the pathogenesis of peritoneal fibrosis, no current large animal model which shares high degree of physiological and anatomical similarities to human is available, limiting their applications on the evaluation of pre-clinical therapeutic efficacy. Here we established for the first time, hypochlorite-induced porcine model of peritoneal fibrosis in 5-week-old piglets. We showed that administration 15-30 mM hypochlorite, a dose- and time-dependent severity of peritoneal fibrosis characterized by mesothelium fragmentation, αSMA+ myofibroblasts accumulation, organ surface thickening and type I collagen deposition were observed. We also demonstrated in vitro using human mesothelial cells that hypochlorite-induced fibrosis was likely due to necrosis, but not programmed apoptosis; besides, overexpression of IL1ß, CX3CL1 and TGFß on the peritoneal mesothelium in current model was detected, similar to observations from peritoneal dialysis-induced peritoneal fibrosis in human patients and earlier reported mouse model. Moreover, our novel antemortem evaluation using laparoscopy provided instant feedback on the progression of organ fibrosis/adhesion which allows immediate adjustments on treatment protocols and strategies in alive individuals that can not and never be performed in other animal models.
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Quimiocina CX3CL1/genética , Interleucina-1beta/genética , Fibrosis Peritoneal/genética , Factor de Crecimiento Transformador beta1/genética , Animales , Colágeno Tipo I/genética , Modelos Animales de Enfermedad , Células Epiteliales/patología , Humanos , Ácido Hipocloroso/toxicidad , Miofibroblastos/metabolismo , Miofibroblastos/patología , Diálisis Peritoneal , Fibrosis Peritoneal/inducido químicamente , Fibrosis Peritoneal/patología , Peritoneo/metabolismo , Peritoneo/patología , Transducción de Señal/genética , PorcinosRESUMEN
In this manuscript, a series of amine tagged short cyclic molecules (cyclopropylamine, cyclobutylamine, cyclopentylamine and cyclohexylamine) were thermally grafted onto p-type silicon (111) hydride surfaces via nucleophilic addition. The chemistries of these grafting were verified via XPS, AFM and sessile droplet measurements. Confocal microscopy and cell viability assay was performed on these surfaces incubated for 24 hours with triple negative breast cancer cells (MDA-MB 231), gastric adenocarcinoma cells (AGS) endometrial adenocarcinoma (Hec1A). All cell types had shown a significant reduction when incubated on these ring-strain cyclic monolayer surfaces than compared to standard controls. The expression level of focal adhesion proteins (vinculin, paxilin, talin and zyxin) were subsequently quantified for all three cell types via qPCR analysis. Cells incubate on these surface grafting were observed to have reduced levels of adhesion protein expression than compared to positive controls (collagen coating and APTES). A potential application of these anti-adhesive surfaces is the maintenance of the chondrocyte phenotype during in-vitro cell expansion. Articular chondrocytes cultured for 6 days on ring strained cyclopropane-modified surfaces was able to proliferate but had maintained a spheroid/aggregated phenotype with higher COL2A1 and ACAN gene expression. Herein, these findings had help promote grafting of cyclic monolayers as an viable alternative for producing antifouling surfaces.
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PURPOSE: This study is aimed at investigating the effect of low-intensity electrical stimulation on the voluntary activation level (VA) and the cortical facilitation/inhibition of quadriceps in people with chronic anterior cruciate ligament lesion. METHODS: Twenty former athletes with unilateral ACL deficiencies (ACL group) and 20 healthy subjects (healthy control group) participated in the study. The quadriceps VA level, motor-evoked potential (MEP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) elicited by transcranial magnetic stimulation were tested before and after 30 minutes of low-intensity electrical stimulation (ES). RESULTS: Before ES, the quadriceps VA in the ACL lesion legs of the ACL group was lower compared to the legs of the healthy control group (P < 0.05). The MEP sizes in the ACL lesion legs and the healthy control were not significantly different. The ACL lesion legs showed lower SICI and higher ICF compared to the healthy control group (P < 0.05). After ES, the quadriceps VA level increased and the SICI-ICF was modulated only in the ACL lesion legs (P < 0.05) but not in the healthy controls. CONCLUSIONS: Low-intensity ES can normalize the modulation of intracortical inhibition and facilitation, thereby ameliorating the activation failure in individuals with ACL lesion.