ABSTRACT
ABSTRACTIntentional forgetting of unwanted information is a crucial cognitive function that is often studied with directed forgetting (DF) procedure, whereby cuing some study materials with Forget (F) instruction impairs their memory compared to cuing with Remember (R) instruction. This study investigates how the nature of information (verbal or pictorial), its semantic significance (meaningful or meaningless), and the degree of prior episodic familiarity influence DF. Before the DF phase, stimuli were familiarised by pre-exposing them 0, 2, or 6 times in a prior preview phase. Finally, memory for all items was assessed with old/new recognition test. Experiment 1 employed words, Experiment 2 utilised fractal images, Experiment 3 featured both meaningful and meaningless object images, and Experiment 4 used words and nonwords. Our results indicate that materials that produced better memory performance are not always harder to intentionally forget. Previewed items showed reduced DF compared to non-previewed items regardless of the nature of information, and meaningless stimuli are challenging to intentionally forget regardless of their degrees of familiarisation unless they are meaningless verbal materials. Collectively, the results highlight the importance of joint consideration of the stimulus format, its meaningfulness, and its episodic familiarity in understanding conditions that interact with intentional forgetting.
Subject(s)
Photic Stimulation , Recognition, Psychology , Humans , Recognition, Psychology/physiology , Male , Female , Young Adult , Adult , Cues , Mental Recall/physiology , Semantics , Memory, EpisodicABSTRACT
Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in reduced dopamine levels in the striatum and eventual onset of motor symptoms. Linalool (3,7-dimethyl-1,6-octadien-3-ol) is a monoterpene in aromatic plants exhibiting antioxidant, antidepressant, and anti-anxiety properties. The objective of this study is to evaluate the neuroprotective impacts of linalool on dopaminergic SH-SY5Y cells, primary mesencephalic and cortical neurons treated with 1-methyl-4-phenylpyridinium ion (MPP+), as well as in PD-like mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Cell viability, α-tubulin staining, western blotting, immunohistochemistry and behavioral experiments were performed. In MPP+-treated SH-SY5Y cells, linalool increased cell viability, reduced neurite retraction, enhanced antioxidant defense by downregulation of apoptosis signaling (B-cell lymphoma 2 (Bcl-2), cleaved caspase-3 and poly ADP-ribose polymerase (PARP)) and phagocyte NADPH oxidase (gp91phox), as well as upregulation of neurotrophic signaling (brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)) and nuclear factor-erythroid 2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. In MPP+-treated primary mesencephalic neurons, linalool enhanced the expressions of tyrosine hydroxylase (TH), Sirtuin 1 (SirT1), and parkin. In MPP+-treated primary cortical neurons, linalool upregulated protein expression of SirT1, γ-Aminobutyric acid type A-α1 (GABAA-α1), and γ-Aminobutyric acid type B (GABAB). In PD-like mice, linalool attenuated the loss of dopamine neurons in SNpc. Linalool improved the motor and nonmotor behavioral deficits and muscle strength of PD-like mice. These findings suggest that linalool potentially protects dopaminergic neurons and improves the impairment symptoms of PD.
Subject(s)
Acyclic Monoterpenes , Neuroblastoma , Neuroprotective Agents , Parkinson Disease , Humans , Mice , Animals , Parkinson Disease/metabolism , Dopaminergic Neurons/metabolism , Antioxidants/metabolism , Odorants , Sirtuin 1/metabolism , Neuroprotective Agents/pharmacology , Neuroblastoma/metabolism , 1-Methyl-4-phenylpyridinium , Muscle Strength , Models, Theoretical , gamma-Aminobutyric Acid/metabolismABSTRACT
BACKGROUND AND AIMS: Peptic ulcer recurrent bleeding occurs in 20% to 30% of patients after standard endoscopic hemostasis, particularly within 4 days after the procedure. The application of additional tranexamic acid (TXA) to the ulcer may enhance hemostasis. This study investigated the effectiveness of TXA powder application on bleeding ulcers during endoscopic hemostasis. METHODS: This study enrolled patients who had peptic ulcer bleeding between March 2022 and February 2023. After undergoing standard endoscopic therapy, the patients were randomly assigned to either the TXA group or the standard group. In the TXA group, an additional 1.25 g of TXA powder was sprayed endoscopically on the ulcer. Both groups then received 3 days of high-dose (8 mg/h) continuous infusion proton pump inhibitor therapy. Second-look endoscopy was conducted on days 3 to 4. The primary end point of early treatment failure was defined as ulcer recurrent bleeding within 4 days or major stigmata of recent hemorrhage on the second-look endoscopy. RESULTS: Sixty patients (30 in each group) with peptic ulcer bleeding and balanced baseline characteristics were randomly assigned to a treatment group. The early treatment failure rate was lower in the TXA group (6.7%) than in the standard group (30%) (P = .042). The freedom from treatment failure periods for 4 and 28 days was significantly longer in the TXA group than in the standard group (P = .023). No adverse events from TXA were recorded. CONCLUSIONS: The precise delivery of topical TXA alongside standard endoscopic hemostasis reduced the early treatment failure rate in patients with bleeding peptic ulcers. (Clinical trial registration number: NCT05248321.).
ABSTRACT
Atopic dermatitis (AD) is a chronic inflammatory and pruritic disease; it can be treated by inhibiting inflammation. Sarcodia suiae sp. is an edible, artificially cultivable red algae with multiple bioactivities. We assessed the anti-inflammatory activity of the ethyl acetate fraction of S. suiae sp. ethanol extract (PD1) on 1-chloro-2,4-dinitrochlorobenzene (DNCB)-induced AD-like lesions. Results show that PD1 alleviated symptoms and significantly decreased clinical dermatitis score. PD1 inhibited serum immunoglobulin E expression and alleviated swelling in the spleen and subiliac lymph nodes. In skin tissues, PD1 alleviated aberrant hyperplasia, decreased epidermal thickness, and decreased the accumulation of mast cells. PD1 mediated the recovery of skin barrier-related proteins, such as claudin-1 and filaggrin. Our study demonstrated that PD1 has anti-inflammatory effects, alleviates AD symptoms, inhibits inflammatory responses in skin tissues, and restores barrier function in DNCB-induced AD mice. These findings reveal that S. suiae sp. extract provides an alternative protective option against AD.
Subject(s)
Dermatitis, Atopic , Rhodophyta , Acetates , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Cytokines/metabolism , Dermatitis, Atopic/chemically induced , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/metabolism , Dinitrochlorobenzene/metabolism , Dinitrochlorobenzene/pharmacology , Dinitrochlorobenzene/therapeutic use , Ethanol/metabolism , Inflammation/metabolism , Mice , Mice, Inbred BALB C , Plant Extracts/metabolism , Rhodophyta/metabolism , SkinABSTRACT
BACKGROUND: An echocardiography-derived calcium score (ECS) has been shown to predict cardiovascular (CV) mortality in the general population but has not been utilized in the dialysis population. METHODS: We conducted a prospective cohort study including 125 prevalent PD patients. Two blinded and independent echocardiographers determined the ECS for each subject at baseline. The primary outcome was the three-point major adverse cardiovascular events (MACE) which is a composite outcome comprising CV death, non-fatal myocardial infarction and non-fatal stroke. The secondary outcome was all-cause mortality. RESULTS: The mean age was 61 ± 13 years. The median follow-up duration was 40 months (range 1-50). Seventy six (60.8%) of the subjects had diabetes mellitus (DM). The median duration of dialysis was 32 (IQR 16-54) months. The incidences of MACE and all-cause mortality were 13.0 per 100 patient-years and 18.3 per 100 patient-years. Multivariate Cox regression analysis identified the following three independent predictors of MACE: ECS (HR 1.253/unit increase in ECS, 95% CI 1.014-1.547, p = .036), DM (HR 2.467, 95% CI 1.014-6.005, p = .047) and pre-existing cardiovascular disease (CVD) (HR 2.441, 95% CI 1.261-4.728, p = .008); and the following two predictors of all-cause mortality: pre-existing CVD (HR 2.156, 95% CI 1.251-3.714, p = .006) and serum albumin (HR 0.887/g/L increase in serum albumin, 95% CI 0.839-0.937, p < .001). CONCLUSION: The ECS appears to be a significant predictor of MACE in PD patients independently of DM and pre-existing CVD.
Subject(s)
Calcium/analysis , Cardiovascular Diseases/diagnostic imaging , Echocardiography , Peritoneal Dialysis , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective StudiesABSTRACT
BACKGROUND: Major advances in management of common pleural diseases have taken place in the past decade. However, pleural diseases are often managed by physicians of diverse training background and research on implementation of new knowledge is scanty. We aim to evaluate the practice pattern in pleural medicine among physicians in Hong Kong, for identification of possible gaps for clinical service improvement. METHODS: The Hong Kong Thoracic Society undertook a cross-sectional questionnaire survey in 2019, targeting clinicians of various subspecialties in internal medicine and levels of experience (basic and higher trainees, specialists) from twelve regional hospitals of diverse service scopes throughout Hong Kong. Respondents were selected by non-probability quota sampling. The questionnaire tool consisted of 46 questions covering diagnostic and therapeutic aspects of common pleural diseases. The responses were anonymous, and analysed independently using SPSS statistics software. RESULTS: The survey collected 129 responses, 47(36%) were from clinicians specialized in respiratory medicine. Majority of the respondents (98%) managed pleural diseases, including performing pleural procedures in their practice. Fifty-five percent of all the respondents had not received any formal training in transthoracic ultrasonography. A significant proportion of clinicians were unaware of pleuroscopy for investigation of exudative pleural effusion, indwelling pleural catheter for recurrent malignant pleural effusion, and combined intra-pleural Alteplase plus DNase for treatment of pleural infection (30%, 15% and 70% of non-respiratory clinicians respectively). Significant heterogeneity was found in the management of pleural infection, malignant pleural effusion and pneumothorax among respiratory versus non-respiratory clinicians. Contributing factors to the observed heterogeneity included lack of awareness or training, limited accessibility of drugs, devices, or dedicated service support. CONCLUSION: Significant heterogeneity in management of pleural diseases was observed among medical clinicians in Hong Kong. Continuous medical education and training provision for both specialists and non-specialists has to be strengthened to enhance the implementation of advances, improve quality and equity of healthcare provision in pleural medicine.
Subject(s)
Pleural Diseases , Pleural Effusion, Malignant , Humans , Pleural Effusion, Malignant/therapy , Cross-Sectional Studies , Hong Kong , Tissue Plasminogen Activator , Surveys and Questionnaires , Pleural Diseases/diagnosis , Pleural Diseases/therapy , DeoxyribonucleasesABSTRACT
With-no-lysine (WNK) kinases regulate renal sodium-chloride cotransporter (NCC) to maintain body sodium and potassium homeostasis. Gain-of-function mutations of WNK1 and WNK4 in humans lead to a Mendelian hypertensive and hyperkalemic disease pseudohypoaldosteronism type II (PHAII). X-ray crystal structure and in vitro studies reveal chloride ion (Cl-) binds to a hydrophobic pocket within the kinase domain of WNKs to inhibit its activity. The mechanism is thought to be important for physiological regulation of NCC by extracellular potassium. To test the hypothesis that WNK4 senses the intracellular concentration of Cl- physiologically, we generated knockin mice carrying Cl--insensitive mutant WNK4. These mice displayed hypertension, hyperkalemia, hyperactive NCC, and other features fully recapitulating human and mouse models of PHAII caused by gain-of-function WNK4. Lowering plasma potassium levels by dietary potassium restriction increased NCC activity in wild-type, but not in knockin, mice. NCC activity in knockin mice can be further enhanced by the administration of norepinephrine, a known activator of NCC. Raising plasma potassium by oral gavage of potassium inactivated NCC within 1 hour in wild-type mice, but had no effect in knockin mice. The results provide compelling support for the notion that WNK4 is a bona fide physiological intracellular Cl- sensor and that Cl- regulation of WNK4 underlies the mechanism of regulation of NCC by extracellular potassium.
Subject(s)
Chlorides/metabolism , Protein Serine-Threonine Kinases/physiology , Animals , Mice , Mice, Transgenic , Potassium/administration & dosage , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Pseudohypoaldosteronism/geneticsABSTRACT
Bronchoscopic interventions (BIs) and airway management for bronchoscopy are exceptionally high-risk procedures not only for anesthesiologists, pulmonologists, but also for nursing staff because they expose nurses to COVID-19-containing droplets. However, perioperative changes can be made to the anesthetic management for nonintubated BIs to minimize the spread of COVID-19.
Subject(s)
Anesthetics , COVID-19 , Humans , Pandemics , SARS-CoV-2ABSTRACT
Background: The COVID-19 pandemic has negatively impacted the eating behaviours of people especially fruits and vegetable intake. No study has addressed the fruits and vegetables intake during the COVID-19 in Malaysia. Aim: to assess the daily intake of fruits and vegetables among Malaysian adults during the COVID-19 outbreak, perceived changes in intake, as well as factors associated with the changes in intake. Methods: A cross-sectional study was conducted through online platforms and a total of 506 participants were recruited. Semi food-frequency questionnaires were used to assess participants' fruit and vegetable intake. Socio-demographics information, knowledge, attitude and practices (KAP) of fruits and vegetables were collected. All statistical analyses were performed using SPSS. Results: The majority of participants (99.8%) did not achieve the recommended five servings per day, in which they consumed an average of 0.84 servings of fruits and vegetables per day. 46.4% of participants reported no changes in intake compared to before the outbreak. Fruits and vegetables intake was associated with physical activity level, knowledge, and beliefs of foods that may prevent/cure COVID-19. Binary logistic regression identified two significant risk factors of daily fruits and vegetables intake namely, being a non-Chinese (AOR = 1.905, 95% CI = 1.114-3.257) and having good practices scores (AOR = 2.543, 95% CI = 1.611-4.015). Conclusion: The study found a low daily intake of fruits and vegetables. The findings suggested that nutritional interventions are necessary to improve awareness on consuming more fruits and vegetables to improve overall health.
Subject(s)
COVID-19 , Vegetables , Adult , Humans , Fruit , COVID-19/epidemiology , COVID-19/prevention & control , Cross-Sectional Studies , Pandemics , Feeding Behavior , Surveys and Questionnaires , DietABSTRACT
Proper growth and patterning of blood vessels are critical for embryogenesis. Chemicals or environmental hormones may interfere with vascular growth and cause developmental defects. Nitrobenzoate-based compounds have been demonstrated to have a wide range of biological and pharmacological functions, leading to the development of numerous 4-nitrobenzoate derivatives for clinical application. In this study, we tested a novel nitrobenzoate-derived compound, X8, and investigated its effects on vascular development using zebrafish as a model organism. We first determined the survival rate of embryos after the addition of exogenous X8 (0.5, 1, 3, 5, and 10 µM) to the fish medium and determined a sublethal dose of 3 µM for use in further assays. We used transgenic fish to examine the effects of X8 treatment on vascular development. At 25-32 h postfertilization (hpf), X8 treatment impaired the growth of intersegmental vessels (ISVs) and caudal vein plexuses (CVPs). Moreover, X8-treated embryos exhibited pericardial edema and circulatory defects at 60-72 hpf, suggesting the effects of X8 in vasculature. Apoptosis tests showed that the vascular defects were likely caused by the inhibition of proliferation and migration. To investigate the molecular impacts underlying the defects in the vasculature of X8-treated fish, the expression levels of vascular markers, including ephrinb2, mrc1, and stabilin, were assessed, and the decreased expression of those genes was detected, indicating that X8 inhibited the expression of vascular genes. Finally, we showed that X8 treatment disrupted exogenous GS4012-induced angiogenesis in Tg(flk:egfp) zebrafish embryos. In addition, vascular defects were enhanced during cotreatment with X8 and the VEGFR2 inhibitor SU5416, suggesting that X8 treatment causes vascular defects mediated by disruption of VEGF/VEGFR2 signaling. Collectively, our findings indicate that X8 could be developed as a novel antiangiogenic agent.
Subject(s)
Neovascularization, Physiologic , Zebrafish , Animals , Animals, Genetically Modified , Embryo, Nonmammalian/metabolism , Neovascularization, Physiologic/genetics , Nitrobenzoates , Signal Transduction , Zebrafish/genetics , Zebrafish/metabolism , Zebrafish Proteins/metabolismABSTRACT
Inflammation is a major cause of skeletal muscle atrophy in various diseases. 2-Hydroxy-4'-methoxychalcone (AN07) is a chalcone-based peroxisome-proliferator-activated receptor gamma (PPARγ) agonist with various effects, such as antiatherosclerosis, anti-inflammation, antioxidative stress, and neuroprotection. In this study, we examined the effects of AN07 on protein homeostasis pathway and mitochondrial function in inflammation-associated myotube atrophy induced by lipopolysaccharides (LPS). We found that AN07 significantly attenuated NF-κB activation, inflammatory factors (TNF-α, IL-1ß, COX-2, and PGE2), Nox4 expression, and reactive oxygen species levels in LPS-treated C2C12 myotubes. Moreover, AN07 increased SOD2 expression and improved mitochondrial function, including mitochondrial membrane potential and mitochondrial oxygen consumption rate. We also demonstrated that AN07 attenuated LPS-induced reduction of myotube diameter, MyHC expression, and IGF-1/IGF-1R/p-Akt-mediated protein synthesis signaling. Additionally, AN07 downregulated LPS-induced autophagy-lysosomal protein degradation molecules (LC3-II/LC3-I and degraded p62) and ubiquitin-proteasome protein degradation molecules (n-FoxO1a/MuRF1/atrogin-1). However, the regulatory effects of AN07 on protein synthesis and degradation signaling were inhibited by the IGF-1R inhibitor AG1024 and the PI3K inhibitor wortmannin. In addition, the PPARγ antagonist GW9662 attenuated the effects of AN07 against LPS-induced inflammation, oxidation, and protein catabolism. In conclusion, our findings suggest that AN07 possesses protective effects on inflammation-induced myotube atrophy and mitochondrial dysfunction.
Subject(s)
Chalcone , Chalcones , Humans , Lipopolysaccharides/adverse effects , Phosphatidylinositol 3-Kinases/metabolism , PPAR gamma/metabolism , Chalcones/pharmacology , Chalcones/metabolism , Chalcone/metabolism , Muscular Atrophy/chemically induced , Muscular Atrophy/drug therapy , Muscular Atrophy/metabolism , Muscle Fibers, Skeletal/metabolism , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/metabolismABSTRACT
Objectives: Recent studies revealed the neuroprotective effects of naringenin (NGEN), a common dietary bioflavonoid contained in citrus fruits. However, there are limited data on its protection against methylglyoxal (MG), the most potent precursor of advanced glycation end-products. The present study was to investigate the protection of NGEN on MG-induced neurotoxicity and the involvement of insulin-like growth factor 1 receptor (IGF-1R) signaling. Methods: NSC34 motor neuron-like cells was used. Cell viability was measured by MTT assay. Protein expressions were analyzed by western blots. Morphological changes of neurites were observed by an inverted microscope. Reactive oxygen species (ROS) production and apoptotic cell numbers were measured by flow cytometer. Glutathione (GSH) level and superoxide dismutase (SOD) activity were measured by ELISA. Results: >NGEN attenuated ROS production and increased GSH level, SOD activity and nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear expression in MG-treated NSC34 cells. NGEN also increased neurite length and enhanced IGF-1R and p-Akt in MG-treated NSC34 cells. Furthermore, NGEN attenuated MG-induced apoptotic death accompanied with down-regulation of cleaved-poly (ADP-ribose) polymerase (PARP) and up-regulation of B-cell lymphoma-2 (Bcl-2). However, AG1024, an IGF-1R antagonist, attenuated the anti-oxidative and anti-apoptotic effects of NGEN in MG-treated cells. Discussion: The present results demonstrated that NGEN decreased neuronal apoptosis and improved antioxidant defense in MG-treated NSC34 cells. Moreover, IGF-1R-mediated antioxidant defense plays an important role in this protective mechanism. These findings suggest the potential benefits of NGEN on the prevention of MG-induced or diabetes/hyperglycemia-related neurotoxicity. In vivo studies are needed for further confirmation on NGEN-mediated neuroprotection.
Subject(s)
Antioxidants/administration & dosage , Apoptosis/drug effects , Flavanones/administration & dosage , Motor Neurons/drug effects , Neurites/drug effects , Neuroprotective Agents/administration & dosage , Pyruvaldehyde/toxicity , Receptor, IGF Type 1/metabolism , Animals , Cell Line, Tumor , Cell Survival/drug effects , Mice , Motor Neurons/metabolism , Oxidative Stress/drug effectsABSTRACT
Kynurenic acid (KYNA, 4-oxoquinoline-2-carboxylic acid), an intermediate of the tryptophan metabolism, has been recognized to exert different neuroactive actions; however, the need of how it or its aminoalkylated amide derivative N-(2-(dimethylamino)ethyl)-3-(morpholinomethyl)-4-oxo-1,4-dihydroquinoline-2-carboxamide (KYNA-A4) exerts any effects on ion currents in excitable cells remains largely unmet. In this study, the investigations of how KYNA and other structurally similar KYNA derivatives have any adjustments on different ionic currents in pituitary GH3 cells and hippocampal mHippoE-14 neurons were performed by patch-clamp technique. KYNA or KYNA-A4 increased the amplitude of M-type K+ current (IK(M)) and concomitantly enhanced the activation time course of the current. The EC50 value required for KYNA- or KYNA-A4 -stimulated IK(M) was yielded to be 18.1 or 6.4 µM, respectively. The presence of KYNA or KYNA-A4 shifted the relationship of normalized IK(M)-conductance versus membrane potential to more depolarized potential with no change in the gating charge of the current. The voltage-dependent hysteretic area of IK(M) elicited by long-lasting triangular ramp pulse was observed in GH3 cells and that was increased during exposure to KYNA or KYNA-A4. In cell-attached current recordings, addition of KYNA raised the open probability of M-type K+ channels, along with increased mean open time of the channel. Cell exposure to KYNA or KYNA-A4 mildly inhibited delayed-rectifying K+ current; however, neither erg-mediated K+ current, hyperpolarization-activated cation current, nor voltage-gated Na+ current in GH3 cells was changed by KYNA or KYNA-A4. Under whole-cell, current-clamp recordings, exposure to KYNA or KYNA-A4 diminished the frequency of spontaneous action potentials; moreover, their reduction in firing frequency was attenuated by linopirdine, yet not by iberiotoxin or apamin. In hippocampal mHippoE-14 neurons, the addition of KYNA also increased the IK(M) amplitude effectively. Taken together, the actions presented herein would be one of the noticeable mechanisms through which they modulate functional activities of excitable cells occurring in vivo.
Subject(s)
Hippocampus/physiology , KCNQ Potassium Channels/drug effects , Kynurenic Acid/pharmacology , Animals , Apamin/pharmacology , Cell Line , Hippocampus/drug effects , Hippocampus/metabolism , Indoles/pharmacology , Kynurenic Acid/chemistry , Membrane Potentials/drug effects , Mice , Patch-Clamp Techniques , Peptides/pharmacology , Pyridines/pharmacology , RatsABSTRACT
Regarding the increased incidence and high mortality rate of malignant melanoma, practical early-detection methods are essential to improve patients' clinical outcomes. In this study, we successfully prepared novel picolinamide-benzamide (18F-FPABZA) and nicotinamide-benzamide (18F-FNABZA) conjugates and determined their biological characteristics. The radiochemical yields of 18F-FPABZA and 18F-FNABZA were 26 ± 5% and 1 ± 0.5%, respectively. 18F-FPABZA was more lipophilic (log P = 1.48) than 18F-FNABZA (log P = 0.68). The cellular uptake of 18F-FPABZA in melanotic B16F10 cells was relatively higher than that of 18F-FNABZA at 15 min post-incubation. However, both radiotracers did not retain in amelanotic A375 cells. The tumor-to-muscle ratios of 18F-FPABZA-injected B16F10 tumor-bearing mice increased from 7.6 ± 0.4 at 15 min post-injection (p.i.) to 27.5 ± 16.6 at 3 h p.i., while those administered with 18F-FNABZA did not show a similarly dramatic increase throughout the experimental period. The results obtained from biodistribution studies were consistent with those derived from microPET imaging. This study demonstrated that 18F-FPABZA is a promising melanin-targeting positron emission tomography (PET) probe for melanotic melanoma.
Subject(s)
Fluorine Radioisotopes , Melanoma, Experimental/diagnostic imaging , Niacinamide , Picolinic Acids , Radiopharmaceuticals , Animals , Cell Line, Tumor , Fluorine Radioisotopes/chemistry , Melanins/metabolism , Melanoma, Experimental/metabolism , Melanoma, Experimental/pathology , Mice , Niacinamide/chemistry , Picolinic Acids/chemistry , Positron-Emission Tomography , Protein Binding , Radiopharmaceuticals/chemistry , Tissue DistributionABSTRACT
BACKGROUND: Beginning from 2015-2016, unprecedented large outbreaks of acute hepatitis A that predominantly affected men who have sex with men (MSM) reemerged across the continents. We assessed the impact of an early initiated hepatitis A virus (HAV) vaccination campaign that targeted MSM living with human immunodeficiency virus (HIV) during the 2015-2017 hepatitis A outbreak in Taiwan. METHODS: First, we ascertained the effectiveness of HAV vaccination for MSM living with HIV using a nested case-control study of 1470 persons living with HIV who were initially HAV-seronegative. We then fitted a model of HAV transmission among MSM, risk-structured by HIV status, to the actual epidemic curve of reported acute hepatitis A cases in Taiwan during 2015-2017. RESULTS: Fifty-five cases of acute hepatitis A were matched to 220 controls. Single-dose and 2-dose HAV vaccination provided protection rates of 96.1% and 97.8% among recipient MSM living with HIV, respectively. Model fitting yielded basic reproductive number estimates of 7.26 (MSM living with HIV) and 3.04 (MSM not living with HIV). In a counterfactual scenario without an HAV vaccination campaign, the outbreak would have involved 7153 hepatitis A cases during 2015-2017 in contrast to the 1352 that were observed. We therefore estimated that the HAV vaccination campaign averted 80.7% (sensitivity analysis, 48.8%-92.7%) of acute hepatitis A cases that would otherwise have occurred by the end of 2017. CONCLUSIONS: The early initiated HAV vaccination campaign, which targeted MSM living with HIV, very effectively curtailed the 2015-2017 hepatitis A outbreak in Taiwan.
Subject(s)
HIV Infections , Hepatitis A , Sexual and Gender Minorities , Case-Control Studies , Disease Outbreaks/prevention & control , HIV Infections/epidemiology , HIV Infections/prevention & control , Hepatitis A/epidemiology , Hepatitis A/prevention & control , Homosexuality, Male , Humans , Immunization Programs , Male , Taiwan/epidemiology , VaccinationABSTRACT
BACKGROUND: The effects of patient sustained self-care behaviors on glycemic control are even greater than the effects of medical treatment, indicating the value of identifying the factors that influence self-care behaviors. To date, these factors have not been placed in a single model to clarify the critical path affecting self-care behaviors. The aims of this study were to explore the relationships of these factors and the differences in patient preference for medical decision-making. METHODS: A cross-sectional study was conducted among outpatients with type 2 diabetes at a regional teaching hospital. Purposive sampling was adopted to recruit 316 eligible patients via self-administered questionnaires. Partial least squares structural equation modeling was used for analysis. RESULTS: Significant direct pathways were identified from health literacy to self-efficacy, patient empowerment, and self-care behaviors; from self-efficacy to self-care behaviors; and from patient empowerment to self-care behaviors. Indirect pathways were from health literacy to self-care behaviors via self-efficacy or patient empowerment. The pathway from health literacy to self-efficacy was significantly stronger in those preferring shared decision-making than in those who preferred physician decision-making. CONCLUSIONS: Health literacy is a critical factor in improving self-care behaviors in patients with type 2 diabetes, and the effect of health literacy on self-efficacy was more significant in the shared decision-making than in the physician decision-making. Therefore, developing an effective health strategy to strengthen health literacy awareness and designing friendly, diverse health literacy materials, and application tools is the most important factor to facilitate self-care behaviors in this population.
Subject(s)
Diabetes Mellitus, Type 2 , Health Literacy , Self Care , Aged , Clinical Decision-Making , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , PatientsABSTRACT
BACKGROUND: Exercise training has positive effects on the management of cardiometabolic conditions. Little is known about the effectiveness of home-based telehealth exercise training programs among patients with cardiometabolic multimorbidity, which is associated with functional decline and decreased health-related quality of life. OBJECTIVE: The aim of this study was to determine the effectiveness of a 12-week home-based telehealth exercise training program designed to increase physical activity and exercise capacity and improve health-related quality of life in patients with cardiometabolic multimorbidity. METHODS: A randomized controlled trial was conducted. Fifty eligible patients with 2 or more cardiometabolic conditions from outpatient clinics of a medical center in Northern Taiwan were randomized to either an experimental group (EG; received a 12-week home-based telehealth exercise training program) or a control group (CG; maintained usual lifestyles). The home-based telehealth exercise training program consisted of 36 individualized home-based exercise training sessions and a weekly reminder for maintenance of exercise and providing patient support. Amounts of physical activity, exercise capacity, and health-related quality of life were assessed at baseline and 12 weeks. Generalized estimating equations were used to examine the intervention effects via the interaction of time and group. RESULTS: The EG had higher amounts of physical activity (ß = 1333, P = .004) and moderate-intensity physical activity (ß = 330, P = .04) than the CG after the intervention. The EG had increased exercise capacity (VO2peak, ß = 4.43, P = .04), as well as improved health-related quality of life (physical function, ß = 7.55, P = .03; and physical component summary, ß = 4.42, P = .03) compared with those in the CG. CONCLUSIONS: A 12-week home-based telehealth exercise training program is feasible and effective in increasing amounts of physical activity, elevating exercise capacity, and improving health-related quality of life in patients with cardiometabolic multimorbidity.
Subject(s)
Cardiac Rehabilitation , Cardiovascular Diseases , Exercise Therapy , Metabolic Diseases/rehabilitation , Telemedicine , Adult , Aged , Exercise , Exercise Tolerance , Female , Humans , Male , Middle Aged , Multimorbidity , Oxygen Consumption , Quality of LifeABSTRACT
Adequate barrier pressure (BrP), calculated by subtracting intragastric pressure (IGP) from lower esophageal sphincter pressure (LESP), is believed to prevent gastroesophageal regurgitation (GER). However, the occurrence of intraoperative GER, the height and acidity it reached, have rarely been demonstrated simultaneously along with BrP. In this study, we developed preattached multichannel intraluminal impedance monitoring combined with pH-metry (the gold standard for detecting both height and acidity) on a solid-state manometry to continuously detect intraoperative GER as well as BrP changes. We used this system to record LESP, IGP, and changes in impedance through multichannel sensors and pH in patients receiving elective gynecological laparoscopy with laparoscopic pneumoperitoneum and Trendelenburg (LPT) positioning. Changes in BrP were analyzed at three time points (T1: before LPT; T2: during LPT when LESP reached its peak; and T3: after the offset of LPT). Our results indicated that this preattached experimental setup is feasible for intraoperative applications. GER was not detected in our patients throughout LPT. The mean LESP at T2 (23.22 mmHg) was significantly higher than at T1 (13.23 mmHg), but comparable to that at T3 (18.91 mmHg). The mean IGP (3.24 mmHg) at T2 was significantly higher than at T1 and T3 (- 6.10 and - 2.25 mmHg, respectively). The mean BrP scores were comparable from T1 to T3 (T1: 19.34 mmHg; T2: 19.98 mmHg; T3: 21.16 mmHg). Based on our results, the proposed setup is helpful for intraoperative monitoring and management of patients at high risk of GER.
Subject(s)
Anesthesiology/methods , Electric Impedance , Esophagus/physiopathology , Laryngopharyngeal Reflux/diagnosis , Manometry/instrumentation , Adult , Calibration , Equipment Design , Female , Humans , Hydrogen-Ion Concentration , Insufflation , Laparoscopy , Manometry/methods , Middle Aged , Pressure , Reproducibility of Results , Young AdultABSTRACT
Background: Honokiol (HNK), a dimer of allylphenol obtained from the bark of Magnolia officinalis was demonstrated to exert an array of biological actions in different excitable cell types. However, whether or how this compound can lead to any perturbations on surface-membrane ionic currents remains largely unknown. Methods: We used the patch clamp method and found that addition of HNK effectively depressed the density of macroscopic hyperpolarization-activated cation currents (Ih) in pituitary GH3 cells in a concentration-, time- and voltage-dependent manner. By the use of a two-step voltage protocol, the presence of HNK (10 µM) shifted the steady-state activation curve of Ih density along the voltage axis to a more negative potential by approximately 11 mV, together with no noteworthy modification in the gating charge of the current. Results: The voltage-dependent hysteresis of Ih density elicited by long-lasting triangular ramp pulse was attenuated by the presence of HNK. The HNK addition also diminished the magnitude of deactivating Ih density elicited by ramp-up depolarization with varying durations. The effective half-maximal concentration (IC50) value needed to inhibit the density of Ih or delayed rectifier K+ current identified in GH3 cells was estimated to be 2.1 or 6.8 µM, respectively. In cell-attached current recordings, HNK decreased the frequency of spontaneous action currents. In Rolf B1.T olfactory sensory neurons, HNK was also observed to decrease Ih density in a concentration-dependent manner. Conclusions: The present study highlights the evidence revealing that HNK has the propensity to perturb these ionic currents and that the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel is proposed to be a potential target for the in vivo actions of HNK and its structurally similar compounds.
Subject(s)
Biphenyl Compounds/pharmacology , Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/drug effects , Lignans/pharmacology , Magnolia/chemistry , Animals , Cell Line , Membrane Potentials/drug effects , Patch-Clamp Techniques , Plant Extracts/chemistry , RatsABSTRACT
UCL-2077 (triphenylmethylaminomethyl)pyridine) was previously reported to suppress slow afterhyperpolarization in neurons. However, the information with respect to the effects of UCL-2077 on ionic currents is quite scarce. The addition of UCL-2077 decreased the amplitude of erg-mediated K+ current (IK(erg)) together with an increased deactivation rate of the current in pituitary GH3 cells. The IC50 and KD values of UCL-2077-induced inhibition of IK(erg) were 4.7 and 5.1 µM, respectively. UCL-2077 (10 µM) distinctly shifted the midpoint in the activation curve of IK(erg) to less hyperpolarizing potentials by 17 mV. Its presence decreased the degree of voltage hysteresis for IK(erg) elicitation by long-lasting triangular ramp pulse. It also diminished the probability of the opening of intermediate-conductance Ca2+-activated K+ channels. In cell-attached current recordings, UCL-2077 raised the frequency of action currents. When KCNH2 mRNA was knocked down, a UCL-2077-mediated increase in AC firing was attenuated. Collectively, the actions elaborated herein conceivably contribute to the perturbating effects of this compound on electrical behaviors of excitable cells.