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Introduction: Elucidating the enduring effects of childhood social capital is vital for shaping future well-being. Here, we investigate the impact of childhood social capital (SC) and parental engagement on adult psychological well-being and cognitive performance. Methods: Utilizing a cohort of 292 Japanese university students, we assessed the influences of SC and parental time during childhood on adult outcomes. Participants retrospectively reported their early childhood experiences, focusing on social interactions and parental involvement. Results: Our findings reveal a significant positive correlation between childhood SC and adult subjective well-being, particularly in its positive dimensions. Additionally, maternal involvement during childhood is associated with cognitive abilities in adulthood, as measured by Raven's Advanced Progressive Matrices. Hierarchical multiple linear regression analysis highlights the substantial impact of childhood SC on adult well-being, elucidating the intricate interplay between social and parental contributions to developmental trajectories. Discussion: These results highlight the crucial roles of both parental and non-parental figures in fostering social, emotional, and cognitive development from childhood to adulthood, underscoring the importance of nurturing supportive relationships throughout early life to promote positive developmental outcomes.
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INTRODUCTION: The underlying risks of asymptomatic embolization during high-power short-duration (HPSD) ablation for atrial fibrillation remain unclear. We aimed to evaluate microembolic signals (MESs) during HPSD ablation with power settings of 50 and 90 W in comparison with those during cryoballoon (CB) ablation using a novel carotid ultrasound-Doppler system that classifies solid and air bubble signals using real-time monitoring. METHODS AND RESULTS: Forty-seven patients underwent HPSD ablation using radiofrequency (RF), and 13 underwent CB ablation. MESs were evaluated using a novel pastable soft ultrasound probe equipped with a carotid ultrasound during pulmonary vein isolation. We compared the detailed MESs and their timing between RF and CB ablations. The number of MESs and solid signals were significantly higher in the RF group than in CB group (209 ± 229 vs. 79 ± 32, p = .047, and 83 ± 89 vs. 28 ± 17, p = .032, respectively). In RF ablation, the number of MESs, solid, and bubble signals per ablation point, or per second, was significantly higher at 90 W than at 50 W ablation. The MESs, solid, and bubble signals were detected more frequently in the bottom and anterior walls of the left pulmonary vein (LPV) ablation. In contrast, many MESs were observed before the first CB application and decreased chronologically as the procedure progressed. Signals were more prevalent during the CB interval rather than during the freezing time. Among the 28 patients, 4 exhibited a high-intensity area on postbrain magnetic resonance imaging (MRI). The MRI-positive group showed a trend of larger signal sizes than did the MRI-negative group. CONCLUSION: The number of MESs was higher in the HPSD RF group than in the CB group, with this risk being more pronounced in the 90 W ablation group. The primary detection site was the anterior wall of the LPV in RF and the first interval in CB ablation.
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Fibrilación Atrial , Criocirugía , Venas Pulmonares , Humanos , Venas Pulmonares/cirugía , Venas Pulmonares/diagnóstico por imagen , Venas Pulmonares/fisiopatología , Fibrilación Atrial/cirugía , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/fisiopatología , Criocirugía/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Factores de Tiempo , Resultado del Tratamiento , Ablación por Catéter/efectos adversos , Valor Predictivo de las Pruebas , Factores de Riesgo , Ultrasonografía Doppler , Arterias Carótidas/diagnóstico por imagen , Arterias Carótidas/cirugía , Estudios Retrospectivos , Enfermedades Asintomáticas , Ultrasonografía de las Arterias CarótidasRESUMEN
Introduction: Excessive alcohol consumption leads to a myriad of detrimental health effects, including alcohol-associated liver disease (ALD). Unfortunately, no available treatments exist to combat the progression of ALD beyond corticosteroid administration and/or liver transplants. Dihydromyricetin (DHM) is a bioactive polyphenol and flavonoid that has traditionally been used in Chinese herbal medicine for its robust antioxidant and anti-inflammatory properties. It is derived from many plants, including Hovenia dulcis and is found as the active ingredient in a variety of popular hangover remedies. Investigations utilizing DHM have demonstrated its ability to alleviate ethanol-induced disruptions in mitochondrial and lipid metabolism, while demonstrating hepatoprotective activity. Methods: Female c57BL/6J mice (n = 12/group) were treated using the Lieber DeCarli forced-drinking and ethanol (EtOH) containing liquid diet, for 5 weeks. Mice were randomly divided into three groups: (1) No-EtOH, (2) EtOH [5% (v/v)], and (3) EtOH [5% (v/v)] + DHM (6 mg/mL). Mice were exposed to ethanol for 2 weeks to ensure the development of ALD pathology prior to receiving dihydromyricetin supplementation. Statistical analysis included one-way ANOVA along with Bonferroni multiple comparison tests, where p ≤ 0.05 was considered statistically significant. Results: Dihydromyricetin administration significantly improved aminotransferase levels (AST/ALT) and reduced levels of circulating lipids including LDL/VLDL, total cholesterol (free cholesterol), and triglycerides. DHM demonstrated enhanced lipid clearance by way of increased lipophagy activity, shown as the increased interaction and colocalization of p62/SQSTM-1, LC3B, and PLIN-1 proteins. DHM-fed mice had increased hepatocyte-to-hepatocyte lipid droplet (LD) heterogeneity, suggesting increased neutralization and sequestration of free lipids into LDs. DHM administration significantly reduced prominent pro-inflammatory cytokines commonly associated with ALD pathology such as TNF-α, IL-6, and IL-17. Discussion: Dihydromyricetin is commercially available as a dietary supplement. The results of this proof-of-concept study demonstrate its potential utility and functionality as a cost-effective and safe candidate to combat inflammation and the progression of ALD pathology.
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A dimeric molecule, di-5(3FM-C4T), with fluoro-substituted mesogenic cores composed of three-aromatic rings and linked by a pentamethylene spacer is prepared. Di-5(3FM-C4T) forms the ferroelectric nematic (NF), ferroelectric smectic-A (SmAPF), and polar isotropic (IsoP) phases. The NF phase is composed of molecules in U-shaped conformation that behave like polar rod-like molecules. The reversal spontaneous polarization (Ps) is approximately 8 µC cm-2, which is extremely large and reflects the huge dipole moment (11.2 D) of the one-side mesogenic core. On the other hand, the SmAPF phase is formed by bent-shaped molecules. The NF-SmAPF phase transition thus follows the conformational change of molecules. The reversal Ps of the SmAPF phase is around 4 µC cm-2, which is half of that in the NF phase, and this is an expected value from the bent shape of the molecules. It is interesting that the highest temperature IsoP phase still exhibits the polar structure and possibly retains some polar aggregation of molecules in small domains. The three polar phases exhibit the dielectric mode due to the collective polarization fluctuation at around 100 Hz, giving the high dielectric constant over 8000.
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The concept of complex and high-risk indicated procedures using percutaneous coronary intervention (CHIP-PCI) has recently been defined. However, few studies have investigated the prognosis of patients after CHIP-PCI. We enrolled 322 consecutive patients who underwent CHIP-PCI. CHIP-PCI was defined as a procedure satisfying at least one criterion each for both patient and procedure characteristics, as follows: patient characteristics [age ≥ 75 years old, low left ventricular ejection fraction (LVEF), diabetes mellitus, acute coronary syndrome, previous coronary artery bypass surgery, peripheral arterial disease, severe chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), and severe valvular disease] and procedure characteristics [unprotected left main disease, degenerated saphenous or radial artery grafts, severely calcified lesions, last patent conduit, chronic total occlusions, multivessel disease, and use of mechanical circulatory support]. On Kaplan-Meier analysis, 1-, 2-, and 3-year survival rates following CHIP-PCI was 93.8%, 89.2%, and 85.4%, respectively. Moreover, on Cox multivariate hazard analysis, age (≥ 75 years old) (hazard ratio: 4.01, 95% confidence interval: 1.92-8.38, P < 0.01), COPD (hazard ratio: 2.95, 95% confidence interval: 1.38-6.32, P < 0.01), low LVEF (hazard ratio: 3.35, 95% confidence interval: 1.55-7.22, P < 0.01), severe CKD (hazard ratio: 3.02, 95% confidence interval: 1.44-6.36, P < 0.01), and use of mechanical circulatory support (hazard ratio: 5.97, 95% confidence interval: 2.72-13.10, P < 0.01) remained significant predictors of mortality. In conclusion, we revealed the clinical outcomes after CHIP-PCI. The presence of advanced age, COPD, low LVEF, severe CKD, and mechanical circulatory support use might lead to worse clinical outcomes.
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Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Anciano , Intervención Coronaria Percutánea/métodos , Puente de Arteria Coronaria , Volumen Sistólico , Resultado del Tratamiento , Función Ventricular Izquierda , Enfermedad de la Arteria Coronaria/cirugía , Factores de RiesgoRESUMEN
BACKGROUND: The distal hemisphere of a balloon is generally cooled during cryoapplication. However, a wide ablation area can be acquired after cryoballoon ablation. This study aimed to evaluate the extent of ice formation on two types of balloon surfaces through experimental and simulation studies. METHODS: A standard cryoballoon (SCB; Arctic Front Advance Pro, Medtronic) and novel cryoballoon (NCB; POLARx, Boston Scientific) were frozen for 240 s in 36 °C normal saline solution to observe ice formation on the balloon surface. Pieces of porcine tissue were placed between the upper and lower sides of the balloon, and the balloon was frozen in the horizontal direction for 240 s in 20 attempts (10 for SCB and NCB each). The measured areas of ice formation were evaluated and compared between the upper and lower sides of each balloon. RESULTS: Ice formation was greater on the lower side of the balloon than on the upper side. A larger area of ice formation in the tissue slab was observed on the lower side than on the upper side in both balloons, and the ice formation extended to the proximal hemisphere on the lower side of the balloon. The ice formation area in the NCB was significantly larger than that in SCB. CONCLUSIONS: Ice formation was significantly greater on the lower side of the cryoballoon than on the upper side and extended to the proximal hemisphere of the balloon, which might facilitate the acquisition of a wide ablation area on the left atrial posterior wall after cryoballoon ablation. Different ice formation after cryoballoon ablation Greater ice formation on the lower side of cryoballoon and an extensive ice formation in the proximal hemisphere, especially in novel cryoballoon.
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Fibrilación Atrial , Ablación por Catéter , Criocirugía , Venas Pulmonares , Animales , Porcinos , Hielo , Fibrilación Atrial/cirugía , Atrios Cardíacos/cirugía , Venas Pulmonares/cirugía , Resultado del TratamientoRESUMEN
We have previously reported social isolation induces anxiety-like behavior, cognitive decline, and reduction in brain ATP levels in mice. These changes were ameliorated by treatment with dihydromyricetin (DHM), a compound that positively modulates γ-aminobutyric A (GABAA) receptor. To gain further insight into the subcellular mechanisms underlying these changes, we utilized a social isolation-induced anxiety mouse model and investigated changes in mitochondrial oxidative capacity via the electron transport chain. We found that 4 weeks of social isolation decreased ATP levels by 43% and succinate dehydrogenase capacity by 52% of the control, while daily DHM (2 mg/kg oral) administration restored succinate dehydrogenase capacity. These results suggest that social isolation decreased mitochondrial capacity to generate ATP. DHM can be developed to be a therapeutic against anxiety and mitochondrial stress.
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Disfunción Cognitiva , Succinato Deshidrogenasa , Ratones , Animales , Succinato Deshidrogenasa/uso terapéutico , Ansiedad/tratamiento farmacológico , Disfunción Cognitiva/tratamiento farmacológico , Aislamiento Social , Adenosina TrifosfatoRESUMEN
The quality of the dietary habits of older adults is important for increasing healthy life expectancy. As with other physical senses, the senses of taste and olfaction change with age. In contrast to physical sensations that can be visibly compared with those of other people, taste and olfaction are personal sensations, making it challenging to infer associated changes. This study investigated the characteristics of taste and olfaction in healthy older adults and compared them with those of young adults. In the taste assessment, threshold values were measured using the whole-mouth method with a diagnostic assay kit (Tastedisc). The olfactory assessment measured the overall identification ability using a card-type olfactory identification test kit (Open Essence). Additionally, participants' subjective health awareness was measured using a visual analog scale. The taste and olfactory assessments results showed that the older group had lower overall sensory sensitivity than the young group, and that there was no correlation between taste and olfactory sensitivity in the older group, while a trend was observed in the young group. Moreover, there was no significant difference between the two groups regarding subjective health awareness, indicating that participants in our research considered themselves healthy regardless of age. This suggests that the subjective health awareness of older people in the health promotion class is somehow independent from their sensory ability.
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Trastornos del Olfato , Gusto , Anciano , Autoevaluación Diagnóstica , Promoción de la Salud , Humanos , Trastornos del Olfato/diagnóstico , Olfato , Adulto JovenRESUMEN
Three kinds of bent-shaped dimeric molecules are synthesized by fluorine substitution of C16 molecules, and influences of the substitution on the polar smectic phases are examined. The fluorine-substituted C16 molecules form the SmAPF and SmCAPA phases. The transition temperatures decrease by 20-30 °C without significantly changing the temperature span of the smectic phase, and the switching rates to the ferroelectric state become 5-10 µs, which are fairly shorter than 250 µs of C16. These behaviors are considered to be caused by the decrease in the intermolecular force and the decrease in the viscosity. The anchoring behavior also appears to be different. On the indium tin oxide (ITO)-coated cell, the fluorine-substituted molecules are homogeneously aligned with the bent (polar) axes perpendicular to the surface, while the bent axes of ordinary bent-shaped molecules lie parallel to the surface. This may be attributable to the repulsion between the fluorine and ITO electrodes. Further, the fluorine substitution can increase the dipole moment of the molecule. The largest dipole moment obtained is 7.94 D, and this leads to a huge reversal polarization of 2.42 µC cm-2, which is much higher compared to those reported in the bent-shaped molecules.
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Cristales Líquidos , Electrodos , Flúor , Polímeros , TemperaturaRESUMEN
This study reports the electric switching behaviors and dielectric properties of the ferroelectric smectic-A (SmAPF), anti-ferroelectric smectic-A (SmAPA), anti-ferroelectric SmCAPA, and smectic-A (SmA) phases formed by mixing the bent-shaped dimeric molecules, α,ω-bis(4-alkoxyanilinebenzylidene-4'-carbonyloxy)pentanes. These four phases each show characteristic features. The SmAPF shows a low threshold electric field for ferroelectric switching and a large dielectric strength due to the collective fluctuation mode of dipoles at around 500 Hz. Both the threshold electric field and dielectric strength are strongly dependent on the cell thickness. The threshold field decreases to 0.1 V µm-1, and the dielectric strength increases up to a huge value of 10,000 as the cell thickness increases up to 80 µm. The SmAPA also shows a similar collective mode at around 2 kHz with a relatively small dielectric strength (around 200), which may be induced by the anti-phase rotation of dipoles in adjacent layers. In these collective modes, the dielectric strength is found to be inversely proportional to the switching threshold field. On the other hand, another anti-ferroelectric SmCAPA as well as the paraelectric SmA show only the non-collective mode (i.e., rotational relaxation of individual molecules around their short axes) at a high frequency of around 100 kHz.
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Social isolation induces stress, anxiety, and mild cognitive impairment that could progress towards irreversible brain damage. A probable player in the mechanism of social isolation-induced anxiety is astrocytes, specialized glial cells that support proper brain function. Using a social isolation mouse model, we observed worsened cognitive and memory abilities with reductions of Object Recognition Index (ORI) in novel object recognition test and Recognition Index (RI) in novel context recognition test. Social isolation also increased astrocyte density, reduced astrocyte size with shorter branches, and reduced morphological complexity in the hippocampus. Dihydromyricetin, a flavonoid that we previously demonstrated to have anxiolytic properties, improved memory/cognition and restored astrocyte plasticity in these mice. Our study indicates astrocytic involvement in social isolation-induced cognitive impairment as well as anxiety and suggest dihydromyricetin as an early-stage intervention against anxiety, cognitive impairment, and potential permanent brain damage.
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Astrocitos , Disfunción Cognitiva , Animales , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Flavonoles/farmacología , Flavonoles/uso terapéutico , Hipocampo , Ratones , Aislamiento Social/psicologíaRESUMEN
BACKGROUND: Anxiety disorders are the most prevalent mental illnesses in the U.S. and are estimated to consume one-third of the country's mental health treatment cost. Although anxiolytic therapies are available, many patients still exhibit treatment resistance, relapse, or substantial side effects. Further, due to the COVID-19 pandemic and stay-at-home order, social isolation, fear of the pandemic, and unprecedented times, the incidence of anxiety has dramatically increased. Previously, we have demonstrated dihydromyricetin (DHM), the major bioactive flavonoid extracted from Ampelopsis grossedentata, exhibits anxiolytic properties in a mouse model of social isolation-induced anxiety. Because GABAergic transmission modulates the immune system in addition to the inhibitory signal transmission, we investigated the effects of short-term social isolation on the neuroimmune system. METHODS: Eight-week-old male C57BL/6 mice were housed under absolute social isolation for 4 weeks. The anxiety-like behaviors after DHM treatment were examined using elevated plus-maze and open field behavioral tests. Gephyrin protein expression, microglial profile changes, NF-κB pathway activation, cytokine level, and serum corticosterone were measured. RESULTS: Socially isolated mice showed increased anxiety levels, reduced exploratory behaviors, and reduced gephyrin levels. Also, a dynamic alteration in hippocampal microglia were detected illustrated as a decline in microglia number and overactivation as determined by significant morphological changes including decreases in lacunarity, perimeter, and cell size and increase in cell density. Moreover, social isolation induced an increase in serum corticosterone level and activation in NF-κB pathway. Notably, DHM treatment counteracted these changes. CONCLUSION: The results suggest that social isolation contributes to neuroinflammation, while DHM has the ability to improve neuroinflammation induced by anxiety.
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Flavonoles/farmacología , Mediadores de Inflamación/antagonistas & inhibidores , Mediadores de Inflamación/metabolismo , Microglía/efectos de los fármacos , Microglía/metabolismo , Aislamiento Social/psicología , Animales , Ansiedad/metabolismo , Ansiedad/prevención & control , Ansiedad/psicología , Flavonoles/uso terapéutico , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Ratones , Ratones Endogámicos C57BLRESUMEN
We report here the case of a 92-year-old woman with atrial fibrillation bradycardia in which leadless pacemaker implantation was performed with a difficult delivery of the catheter sheath due to an extremely large right atrium. Using a snare technique with correction of the direction of the force on the catheter toward the right ventricle (RV) can result in successful delivery of the pacemaker catheter and stable placement of the pacemaker system in the RV septum. This specific snare technique has the potential to facilitate leadless pacemaker implantation safely in a severely dilated chamber of the heart, making this technique effective to use in clinical practice.
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Fibrilación Atrial/terapia , Bradicardia/terapia , Cateterismo Cardíaco/métodos , Marcapaso Artificial , Implantación de Prótesis/métodos , Anciano de 80 o más Años , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Bradicardia/complicaciones , Bradicardia/diagnóstico , Femenino , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/patología , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/patología , HumanosRESUMEN
Objective The left atrial appendage (LAA) is one of the major sources of cardiac thrombus formation. Three-dimensional transesophageal echocardiography (TEE) made it possible to perform a detailed evaluation of the LAA morphologies. This study aimed to evaluate the clinical implications of the LAA orifice area. Methods A total of 149 patients who underwent TEE without significant valvular disease were studied. The LAA orifice area was measured using three-dimensional TEE. The patients were divided into two groups according to the LAA orifice area (large LAA orifice group, ≥median value, and small LAA orifice group). The clinical characteristics and echocardiographic findings were evaluated. Results The median LAA orifice area among all patients was 4.09 cm2 (interquartile range 2.92-5.40). The large LAA orifice group were older (67.2±10.4 vs. 62.4±15.3 years, p=0.02), more often had hypertension (66.7% vs. 44.6%, p=0.007), and atrial fibrillation (70.7% vs. 39.2%, p<0.001) than the small LAA orifice group. Regarding the TEE findings, the LAA flow velocity was significantly lower (33.7±20.0 vs. 50.2±24.3, p<0.001) and spontaneous echo contrast was more often observed (21.3% vs. 8.1%, p=0.02) in the large LAA orifice group. Multivariate models demonstrated that atrial fibrillation was an independent predictor of the LAA orifice area. In the analysis of atrial fibrillation duration, the LAA orifice area tended to be larger as patients had a longer duration of atrial fibrillation. Conclusion Our findings indicated that a larger LAA orifice area was associated with the presence of atrial fibrillation and high thromboembolic risk based on TEE findings. A continuation of the atrial fibrillation rhythm might lead to the gradual expansion of the LAA orifice.
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Apéndice Atrial , Fibrilación Atrial , Ecocardiografía Tridimensional , Tromboembolia , Apéndice Atrial/diagnóstico por imagen , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico por imagen , Ecocardiografía Tridimensional/métodos , Ecocardiografía Transesofágica/métodos , Humanos , Tromboembolia/complicacionesRESUMEN
In cryoballoon ablation (CBA), a contrast medium is commonly used to confirm balloon occlusion of the pulmonary veins (PVs). However, a contrast medium cannot always be used in patients with renal dysfunction and allergy. The present study aimed to assess the efficacy and safety of CBA without the use of a contrast medium. We retrospectively examined consecutive patients with paroxysmal atrial fibrillation (PAF) who underwent first-time CBA. We compared the procedural results and outcomes in patients for whom a contrast medium was used (contrast group) and those from whom a contrast medium was not used (non-contrast group). In the non-contrast group, we used saline injection on the intracardiac echocardiography and pressure wave monitoring for PV occlusion. Fifty patients (200 PVs) and 22 patients (88 PVs) underwent CBA with and without a contrast medium, respectively. The success rate of PV isolation with CBA alone was 93% and 90% in the non-contrast and contrast groups, respectively (p = 0.40). The fluoroscopy time and nadir temperature were significantly lower in the non-contrast group as compared to that in the contrast group. The recurrence rate 1 year after ablation did not differ between the two groups (18% vs. 18%, p > 0.99). Furthermore, the number of reconnected PVs in patients with recurrence was significantly lower in the non-contrast group than in the contrast group (6% vs. 36%, p = 0.017). In conclusion, CBA using the intracardiac echocardiography and pressure monitoring approach without the use of a contrast medium was safe and efficient.
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Fibrilación Atrial , Ablación por Catéter , Criocirugía , Venas Pulmonares , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Ablación por Catéter/efectos adversos , Criocirugía/efectos adversos , Criocirugía/métodos , Ecocardiografía/métodos , Humanos , Venas Pulmonares/diagnóstico por imagen , Venas Pulmonares/cirugía , Recurrencia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Background: Anxiety disorders are the most prevalent mental illnesses in the U.S. and are estimated to consume one-third of the country's mental health treatment cost. Although anxiolytic therapies are available, many patients still exhibit treatment-resistance, relapse, or substantial side effects. Further, due to the COVID-19 pandemic and stay-at-home order, social isolation, fear of the pandemic, and unprecedented times, the incidence of anxiety has dramatically increased. Previously, we have demonstrated dihydromyricetin (DHM), the major bioactive flavonoid extracted from Ampelopsis grossedentata , exhibits anxiolytic properties in a mouse model of social isolation-induced anxiety. Because GABAergic transmission modulates the immune system in addition to the inhibitory signal transmission, we investigated the effects of short-term social isolation on the neuroimmune system. Methods: Eight-week-old male C57BL/6 mice were housed under absolute social isolation for 4 weeks. The anxiety like behaviors after DHM treatment were examined using elevated plus maze and open field behavioral tests. Gephyrin protein expression, microglial profile changes, NF-κB pathway activation, cytokine level, and serum corticosterone were measured. Results: Socially isolated mice showed increased anxiety levels, reduced exploratory behaviors, and reduced gephyrin levels. Also, a dynamic alteration in hippocampal microglia were detected illustrated as a decline in microglia number and overactivation as determined by significant morphological changes including decreases in lacunarity, perimeter, and cell size and increase in cell density. Moreover, social isolation also induced an increase in serum corticosterone level and activation in NF-κB pathway. Notably, DHM treatment counteracted these changes. Conclusion: The results suggest that social isolation contributes to neuroinflammation, while DHM has the ability to restore neuroinflammatory changes induced by anxiety.
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INTRODUCTION: With regard to short-term outcome in atrial fibrillation (AF), the benefit of cryoballoon ablation (CBA) by pressing a balloon against the earliest pulmonary vein (PV) potential site during PV isolation (earliest potential [EP]-guided CBA) has been previously demonstrated. The present study aimed to evaluate the long-term outcome of the EP-guided CBA. METHODS AND RESULTS: This study included 136 patients from two randomized studies, who underwent CBA for paroxysmal AF for the first time. Patients were randomly assigned to the EP-guided and conventional CBA groups in each study. In the EP-guided CBA group, we pressed a balloon against the EP site when the time-to-isolation (TTI) after cryoapplication exceeded 60 and 45 s in the first and second studies, respectively. We compared the clinical outcomes for 1 year after the procedure between the EP-guided CBA group (68 patients) and the conventional CBA group (68 patients). The primary endpoint was the recurrence of atrial arrhythmia after ablation. No significant differences in baseline characteristics were observed between the two groups. Compared with the conventional CBA group, the EP-guided CBA group had a significantly higher success rate at TTI ≤ 90 s (98.5% vs. 90.0%, p < .001); lower touch-up rate and total cryoapplication; and shorter procedure time, and fluoroscopy time. The recurrence at 1 year after ablation was significantly lower in the EP-guided CBA group than in the conventional CBA group (6.0% vs. 19.4%; p = .019). CONCLUSIONS: The EP-guided CBA approach can facilitate the ablation procedure and achieve low recurrence at 1 year after ablation.
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Fibrilación Atrial , Ablación por Catéter , Criocirugía , Venas Pulmonares , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Ablación por Catéter/efectos adversos , Criocirugía/efectos adversos , Humanos , Venas Pulmonares/diagnóstico por imagen , Venas Pulmonares/cirugía , Ensayos Clínicos Controlados Aleatorios como Asunto , Recurrencia , Resultado del TratamientoRESUMEN
Random conjugations of chemotherapeutics to monoclonal antibodies result in heterogeneous antibody-drug conjugates (ADCs) with suboptimal pharmacological properties. We recently developed a new technology for facile generation of homogeneous ADCs by harnessing human CD38 catalytic domain and its dinucleotide-derived covalent inhibitor, termed ADP-ribosyl cyclase-enabled ADCs (ARC-ADCs). Herein we advance this technology by designing and synthesizing ARC-ADCs with customizable drug-to-antibody ratios (DARs). Through varying numbers and locations of CD38 fused to an antibody targeting human C-type lectin-like molecule-1 (hCLL-1), ARC-ADCs featuring DARs of 2 and 4 were rapidly generated via a single step with cytotoxic monomethyl auristatin F (MMAF) as payloads. In contrast to anti-hCLL-1 ARC-ADC carrying 2 drug molecules, anti-hCLL-1 ARC-ADC with a DAR of 4 shows highly potent activity in killing hCLL-1-positive acute myeloid leukemia (AML) cells both in vitro and in vivo. This work provides novel ADC candidates for combating AML and supports ARC-ADC as a general and versatile approach for producing site-specific ADCs with defined DARs.
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Antineoplásicos , Inmunoconjugados , Leucemia Mieloide Aguda , Preparaciones Farmacéuticas , Anticuerpos Monoclonales , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológicoRESUMEN
Interpersonal physiological synchrony has been shown to play important roles in social activities. While most studies have shed light on the effects of physiological synchrony on recognition of the group state, such as cohesion or togetherness, the effect of physiological synchrony on the recognition of emotional experience has not been adequately researched. In this study, we examined how physiological synchrony is associated with first- and third-person emotion recognition during a joint task. Two participants played a cooperative block-stacking game (Jenga), alternating their roles as player and adviser, while their heart rates were recorded. The participants evaluated their own emotional experience for each turn. Bystanders watched the game to evaluate the players' emotions. Results showed that the players' subjective excitement increased not only with their own heart rate, but also with increased heart rate synchrony with their adviser. Heart rate synchrony between player and adviser also related to increased intensity in perceived excitement from the bystanders. Given that both first- and third-person emotion recognition can have cumulative impacts on a group, the relationship between physiological synchrony and emotion recognition observed in the present study will help deepen understanding of the psychophysiological mechanisms underlying larger group phenomena such as crowd excitement.