RESUMEN
Although complex inflammatory-like alterations are observed around the amyloid plaques of Alzheimer's disease (AD), little is known about the molecular changes and cellular interactions that characterize this response. We investigate here, in an AD mouse model, the transcriptional changes occurring in tissue domains in a 100-µm diameter around amyloid plaques using spatial transcriptomics. We demonstrate early alterations in a gene co-expression network enriched for myelin and oligodendrocyte genes (OLIGs), whereas a multicellular gene co-expression network of plaque-induced genes (PIGs) involving the complement system, oxidative stress, lysosomes, and inflammation is prominent in the later phase of the disease. We confirm the majority of the observed alterations at the cellular level using in situ sequencing on mouse and human brain sections. Genome-wide spatial transcriptomics analysis provides an unprecedented approach to untangle the dysregulated cellular network in the vicinity of pathogenic hallmarks of AD and other brain diseases.
Asunto(s)
Enfermedad de Alzheimer/patología , Análisis de Secuencia de ADN/métodos , Transcriptoma , Enfermedad de Alzheimer/genética , Amiloide/metabolismo , Péptidos beta-Amiloides/genética , Péptidos beta-Amiloides/metabolismo , Animales , Encéfalo/metabolismo , Encéfalo/patología , Proteínas del Sistema Complemento/genética , Proteínas del Sistema Complemento/metabolismo , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Humanos , Lisosomas/genética , Lisosomas/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Vaina de Mielina/genética , Vaina de Mielina/metabolismo , Estrés Oxidativo/genéticaRESUMEN
Wave instability-the process that gives rise to turbulence in hydrodynamics1-represents the mechanism by which a small disturbance in a wave grows in amplitude owing to nonlinear interactions. In photonics, wave instabilities result in modulated light waveforms that can become periodic in the presence of coherent locking mechanisms. These periodic optical waveforms are known as optical frequency combs2-4. In ring microresonator combs5,6, an injected monochromatic wave becomes destabilized by the interplay between the resonator dispersion and the Kerr nonlinearity of the constituent crystal. By contrast, in ring lasers instabilities are considered to occur only under extreme pumping conditions7,8. Here we show that, despite this notion, semiconductor ring lasers with ultrafast gain recovery9,10 can enter frequency comb regimes at low pumping levels owing to phase turbulence11-an instability known to occur in hydrodynamics, superconductors and Bose-Einstein condensates. This instability arises from the phase-amplitude coupling of the laser field provided by linewidth enhancement12, which produces the needed interplay of dispersive and nonlinear effects. We formulate the instability condition in the framework of the Ginzburg-Landau formalism11. The localized structures that we observe share several properties with dissipative Kerr solitons, providing a first step towards connecting semiconductor ring lasers and microresonator frequency combs13.
RESUMEN
The impacts of patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M-rs738409, methylenetetrahydrofolate reductase (MTHFR) Ala222Val-rs1801133, and aldehyde dehydrogenase 2 (ALDH2) Glu504Lys-rs671 on the outcomes of Taiwanese patients with steatotic liver disease (SLD) have remained elusive. An 8-year prospective cohort study of patients with (n = 546) and without (n = 580) SLD (controls) was undertaken in a Taiwanese tertiary care center. The 546 SLD patients comprised 306 (56.0%) men and 240 (44.0%) women with mean ages of 53.3 and 56.4 years, respectively. Compared with the controls, SLD patients had an increased frequency of the PNPLA3 I148M-rs738409 GG genotype (25.5 vs. 5.9%, p = 0.001). Among the SLD patients, 236 (43.1%) suffered cardiovascular events, 52 (9.5%) showed extrahepatic cancers, 13 (2.38%) experienced hepatic events, including hepatocellular carcinoma (n = 3, 0.5%) and liver cirrhosis (n = 8, 1.47%), and none died. The Fibrosis-4 (FIB-4) scores were associated with extrahepatic cancer (hazard ratio [HR] 1.325; 95% confidence interval [CI], 1.038-1.691) and cirrhosis development (HR 1.532; 95% CI, 1.055-2.224), and the PNPLA3 I148M-rs738409 G allele (ß = 0.158, 95% CI, 0.054-0.325) was associated with the FIB-4 score. Stratified analyses showed that the impact of the FIB-4 score on extrahepatic cancer development was evident only in SLD patients with the PNPLA3 I148M-rs738409 GG genotype (HR 1.543; 95% CI, 1.195-1.993) and not in patients with the GC or CC genotype. Moreover, the ALDH2 Glu504Lys-rs671 G allele had a dose-dependent effect on alcoholism, and the MTHFR and ALDH2 genotypes were not significantly associated with SLD patient outcomes. In conclusion, special vigilance should be exercised for emerging extrahepatic cancer in SLD patients with the PNPLA3 I148M-rs738409 GG genotype and high FIB-4 scores.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aldehído Deshidrogenasa Mitocondrial/genética , Carcinoma Hepatocelular/genética , Predisposición Genética a la Enfermedad , Genotipo , Cirrosis Hepática/complicaciones , Cirrosis Hepática/genética , Neoplasias Hepáticas/genética , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/patología , Polimorfismo de Nucleótido Simple , Estudios ProspectivosRESUMEN
Background: Postarrest acute kidney injury (AKI) is a major health burden because it is associated with prolonged hospitalization, increased dialysis requirement, high mortality, and unfavorable neurological outcomes. Managing hemodynamic instability during the early postarrest period is critical; however, the role of quantified vasopressor dependence in AKI development in relation to illness severity remains unclear. Methods: A retrospective, observational cohort study that enrolled 411 non-traumatic adult cardiac arrest survivors without pre-arrest end-stage kidney disease between January 2017 and December 2019, grouped according to their baseline kidney function. The criteria for kidney injury were based on the Kidney Disease: Improving Global Outcomes definition and AKI staging system. The degree of vasopressor dependence within the first 24 h following return of spontaneous circulation (ROSC) was presented using the maximum vasoactive-inotropic score ( VIS max ). Results: Of the 411 patients, 181 (44%) had early AKI after ROSC. Patients with AKI showed an increased risk of in-hospital mortality (adjusted OR [aOR] 5.40, 95% CI 3.36-8.69, p < 0.001) and unfavorable neurological outcome (aOR 5.70, 95% CI 3.45-9.43, p < 0.001) compared to patients without AKI. The risk of adverse outcomes increased with illness severity. Patients with vasopressor support had an increased risk of early AKI. A low VIS max was associated with AKI stage 1-2 (aOR 2.51, 95% CI 1.20-5.24), whereas a high VIS max was associated with an increased risk for AKI stage 3 (aOR 2.46, 95% CI 1.28-4.75). Conclusions: Early AKI is associated with an increased risk of in-hospital mortality and unfavorable neurologic recovery in cardiac arrest survivors. Postarrest VIS max is an independent predictor of the development and severity of AKI following ROSC, regardless of baseline kidney function.
RESUMEN
AIM: The response rate to pioglitazone and the predictive factors for its effects on improving liver biochemistry in patients with steatotic liver disease (SLD) remain elusive, so we aimed to investigate these issues. METHODS: A 3-year prospective cohort study of 126 Taiwanese patients with SLD treated with pioglitazone (15-30 mg/day) was conducted. Phospholipase domain-containing protein 3 I148M rs738409, methylenetetrahydrofolate reductase rs1801133, aldehyde dehydrogenase 2 (ALDH2) rs671 and lipoprotein lipase rs10099160 single nucleotide polymorphisms were assessed in the patients. RESULTS: Of 126 patients, 78 (61.9%) were men, and the mean and median ages were 54.3 and 56.5 years, respectively. Pioglitazone responders were defined as those with decreased alanine aminotransferase (ALT) levels at 6 months post-treatment, and 105 (83.3%) patients were responders. Compared with non-responders, responders were more frequently women and had higher baseline ALT levels. The proportion of patients with the ALDH2 rs671 GG genotype was lower among responders (38.6% vs. 66.6%, p = .028). Female sex [odds ratio (OR): 4.514, p = .023] and baseline ALT level (OR: 1.015, p = .046; cut-off level: ≥82 U/L) were associated with pioglitazone response. Among responders, the liver biochemistry and homeostasis model assessment of insulin resistance improved from 6 to 24 months post-treatment. The total cholesterol levels decreased within 6 months, while increases in high-density lipoprotein cholesterol levels and decreases in triglyceride levels and fibrosis-4 scores were noted only at 24 months post-treatment. The 2-year cumulative incidences of cardiovascular events, cancers and hepatic events were similar between responders and non-responders. CONCLUSIONS: Regarding liver biochemistry, over 80% of Taiwanese patients with SLD had a pioglitazone response, which was positively associated with female sex and baseline ALT levels. Insulin resistance improved as early as 6 months post-treatment, while liver fibrosis improvement was not observed until 24 months post-treatment. The link between the pioglitazone response and the ALDH2 genotype warrants further investigation.
Asunto(s)
Aldehído Deshidrogenasa Mitocondrial , Hipoglucemiantes , Pioglitazona , Polimorfismo de Nucleótido Simple , Humanos , Pioglitazona/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Hipoglucemiantes/uso terapéutico , Resultado del Tratamiento , Aldehído Deshidrogenasa Mitocondrial/genética , Taiwán/epidemiología , Alanina Transaminasa/sangre , Tiazolidinedionas/uso terapéutico , Hígado Graso/tratamiento farmacológico , Hígado Graso/genética , Anciano , Lipoproteína Lipasa/genética , Hígado/efectos de los fármacos , Hígado/patología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicaciones , Genotipo , AdultoRESUMEN
The coupled NO-vibrational peaks [IR νNO 1775 s, 1716 vs, 1668 vs cm-1 (THF)] between two adjacent [Fe(NO)2] groups implicate the electron delocalization nature of the singly O-phenoxide-bridged dinuclear dinitrosyliron complex (DNIC) [Fe(NO)2(µ-ON2Me)Fe(NO)2] (1). Electronic interplay between [Fe(NO)2] units and [ON2Me]- ligand in DNIC 1 rationalizes that "hard" O-phenoxide moiety polarizes iron center(s) of [Fe(NO)2] unit(s) to enforce a "constrained" π-conjugation system acting as an electron reservoir to bestow the spin-frustrated {Fe(NO)2}9-{Fe(NO)2}9-[·ON2Me]2- electron configuration (Stotal = 1/2). This system plays a crucial role in facilitating the ligand-based redox interconversion, working in harmony to control the storage and redox-triggered transport of the [Fe(NO)2]10 unit, while preserving the {Fe(NO)2}9 core in DNICs {Fe(NO)2}9-[·ON2Me]2- [K-18-crown-6-ether)][(ON2Me)Fe(NO)2] (2) and {Fe(NO)2}9-[·ON2Me] [(ON2Me)Fe(NO)2][PF6] (3). Electrochemical studies suggest that the redox interconversion among [{Fe(NO)2}9-[·ON2Me]2-] DNIC 3 â [{Fe(NO)2}9-[ON2Me]-] â [{Fe(NO)2}9-[·ON2Me]] DNIC 2 are kinetically feasible, corroborated by the redox shuttle between O-bridged dimerized [(µ-ONMe)2Fe2(NO)4] (4) and [K-18-crown-6-ether)][(ONMe)Fe(NO)2] (5). In parallel with this finding, the electronic structures of [{Fe(NO)2}9-{Fe(NO)2}9-[·ON2Me]2-] DNIC 1, [{Fe(NO)2}9-[·ON2Me]2-] DNIC 2, [{Fe(NO)2}9-[·ON2Me]] DNIC 3, [{Fe(NO)2}9-[ONMe]-]2 DNIC 4, and [{Fe(NO)2}9-[·ONMe]2-] DNIC 5 are evidenced by EPR, SQUID, and Fe K-edge pre-edge analyses, respectively.
RESUMEN
BACKGROUND AND AIM: Chromoendoscopy with the use of indigo carmine (IC) dye is a crucial endoscopic technique to identify gastrointestinal neoplasms. However, its performance is limited by the endoscopist's skill, and no standards are available for lesion identification. Thus, we developed an artificial intelligence (AI) model to replace chromoendoscopy. METHODS: This pilot study assessed the feasibility of our novel AI model in the conversion of white-light images (WLI) into virtual IC-dyed images based on a generative adversarial network. The predictions of our AI model were evaluated against the assessments of five endoscopic experts who were blinded to the purpose of this study with a staining quality rating from 1 (unacceptable) to 4 (excellent). RESULTS: The AI model successfully transformed the WLI of polyps with different morphologies and different types of lesions in the gastrointestinal tract into virtual IC-dyed images. The quality ratings of the real IC-dyed and AI images did not significantly differ concerning surface structure (AI vs IC: 3.08 vs 3.00), lesion border (3.04 vs 2.98), and overall contrast (3.14 vs 3.02) from 10 sets of images (10 AI images and 10 real IC-dyed images). Although the score depended significantly on the evaluator, the staining methods (AI or real IC) and evaluators had no significant interaction (P > 0.05) with each other. CONCLUSION: Our results demonstrated the feasibility of employing AI model's virtual IC staining, increasing the possibility of being employed in daily practice. This novel technology may facilitate gastrointestinal lesion identification in the future.
Asunto(s)
Inteligencia Artificial , Lesiones Precancerosas , Humanos , Proyectos Piloto , Endoscopía/métodos , Carmin de Índigo , Carmín , Lesiones Precancerosas/diagnóstico por imagenRESUMEN
BACKGROUND: The characteristics of autoimmune hepatitis (AIH) in Asia mostly remain elusive. METHODS: A cohort study of liver biopsy-proven AIH patients was conducted in a tertiary care cancer of Taiwan. RESULTS: From 1999 to 2022, of 13,766 patients who underwent liver biopsy, 150 patients with AIH were enrolled. The female-to-male ratio was 2.26. At baseline, the mean age was 51.09 years, mean alanine aminotransferase level was 494.11 U/L, and 17 (11.3%) had cirrhosis. All except one patient had AIH type 1. The females were older and had higher baseline cirrhosis rates than did the males. The 23-year cumulative incidences of cirrhosis, hepatocellular carcinoma (HCC), mortality/liver transplantation, autoimmune diseases and extrahepatic cancer were 64.2%, 13.3%, 23.4%, 30.7% and 21.2%, respectively. The 1-year, 2-year, 3-year, 5-year, 10-year and 20-year postimmunosuppressive therapy relapse rates were 60%, 78.2%, 81.8%, 89.1%, 94.5% and 100%, respectively. Baseline associations were as follows: alkaline phosphatase (Alk-p) levels with postimmunosuppressive therapy flare [hazard ratio (HR): 1.003; 95% CI HR: 1.000-1.005]; age with HCC (1.072; 1.010-1.138) and all-cause cancer (1.041;1.005-1.079); cirrhosis with mortality/liver transplantation (11.933;1.984-71.787); and antinuclear antibody (ANA) titers with mortality/liver transplantation (1.001;1.000-1.003), cirrhosis (1.001;1.000-1.002), and autoimmune diseases (1.001; 1.000-1.002). CONCLUSION: In an Asian country endemic for viral hepatitis, the female-to-male and baseline cirrhosis rates of AIH patients were lower than expected, while over 60% of the patients eventually developed cirrhosis. The high posttherapy relapse rate warrants cautious monitoring, particularly for patients with high baseline Alk-p levels. Baseline age, cirrhosis status and ANA titers are crucial for outcomes.
Asunto(s)
Hepatitis Autoinmune , Cirrosis Hepática , Neoplasias Hepáticas , Humanos , Hepatitis Autoinmune/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Taiwán/epidemiología , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/mortalidad , Cirrosis Hepática/epidemiología , Cirrosis Hepática/diagnóstico , Trasplante de Hígado/estadística & datos numéricos , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/mortalidad , Estudios de Cohortes , Anciano , Recurrencia , Incidencia , Estudios Retrospectivos , Hígado/patología , Adulto Joven , Inmunosupresores/uso terapéuticoRESUMEN
BACKGROUND: Established protocols for implementing high-quality targeted temperature management (TTM) provide guidance concerning the cooling rate, duration of maintenance, and rewarming speed. However, whether compliant to TTM protocols results in improved survival and better neurological recovery has not been examined. METHODS: A retrospective cohort study enrolled 1141 survivors of non-traumatic adult cardiac arrest with a pre-arrest cerebral performance category (CPC) score of 1-2 from 2015 to 2020 at a tertiary medical center. Of the survivors, 330 patients who underwent TTM were further included. Patients with spontaneous hypothermia (<35 °C) (n = 107) and expired during the TTM (n = 21) were excluded. A total of 202 patients were thus enrolled. One hundred and ten patients underwent TTM that completely complied with the protocol (protocol-complaint group), but 92 patients deviated in some manner from the protocol (protocol non-compliant group). RESULTS: Fifty patients (50%) and 46 patients (50%) in the protocol-compliant and non-compliant groups, respectively, did not survive to hospital discharge. In the protocol-compliant group, 42 patients (38.2%) had favorable neurological recovery, compared with 32 patients (34.8%) in the protocol non-compliant group. After adjusting for age, initial shockable rhythm, witnessed collapse, and cardiopulmonary resuscitation duration, protocol non-compliant was associated with the poor neurological outcomes (aOR 2.44, 95% CI = 1.13-5.25), but not with in-hospital mortality (aOR 1.31, 95% CI = 0.70-2.47). The most common reason for noncompliance was a prolonged duration reaching the target temperature (n = 33, 58.7%). The number of phases of non-compliant was not significantly associated with in-hospital mortality or poor neurological recovery. CONCLUSION: Among cardiac arrest survivors undergoing TTM, those who did not receive TTM that in compliance with the protocol were more likely to experience poor neurological recovery than those whose TTM fully complied with the protocols. The most frequently identified deviation was a prolonged duration to reaching the target temperature.
RESUMEN
The biological mechanisms underpinning learning are unclear. Mounting evidence has suggested that adult hippocampal neurogenesis is involved although a causal relationship has not been well defined. Here, using high-resolution genetic mapping of adult neurogenesis, combined with sequencing information, we identify follistatin (Fst) and demonstrate its involvement in learning and adult neurogenesis. We confirmed that brain-specific Fst knockout (KO) mice exhibited decreased hippocampal neurogenesis and demonstrated that FST is critical for learning. Fst KO mice exhibit deficits in spatial learning, working memory, and long-term potentiation (LTP). In contrast, hippocampal overexpression of Fst in KO mice reversed these impairments. By utilizing RNA sequencing and chromatin immunoprecipitation, we identified Asic4 as a target gene regulated by FST and show that Asic4 plays a critical role in learning deficits caused by Fst deletion. Long-term overexpression of hippocampal Fst in C57BL/6 wild-type mice alleviates age-related decline in cognition, neurogenesis, and LTP. Collectively, our study reveals the functions for FST in adult neurogenesis and learning behaviors.
Asunto(s)
Canales Iónicos Sensibles al Ácido/metabolismo , Folistatina/fisiología , Hipocampo/metabolismo , Neurogénesis , Plasticidad Neuronal , Aprendizaje Espacial/fisiología , Canales Iónicos Sensibles al Ácido/genética , Animales , Cognición , Femenino , Potenciación a Largo Plazo , Masculino , Memoria , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Sinapsis/fisiologíaRESUMEN
BACKGROUND: Phosphorylated Tau (p-Tau), an early biomarker of neuronal damage, has emerged as a promising candidate for predicting neurological outcomes in cardiac arrest (CA) survivors. Despite its potential, the correlation of p-Tau with other clinical indicators remains underexplored. This study assesses the predictive capability of p-Tau and its effectiveness when used in conjunction with other predictors. METHODS: In this single-center retrospective study, 230 CA survivors had plasma and brain computed tomography scans collected within 24 h after the return of spontaneous circulation (ROSC) from January 2016 to June 2023. The patients with prearrest Cerebral Performance Category scores ≥ 3 were excluded (n = 33). The neurological outcomes at discharge with Cerebral Performance Category scores 1-2 indicated favorable outcomes. Plasma p-Tau levels were measured using an enzyme-linked immunosorbent assay, diastolic blood pressure (DBP) was recorded after ROSC, and the gray-to-white matter ratio (GWR) was calculated from brain computed tomography scans within 24 h after ROSC. RESULTS: Of 197 patients enrolled in the study, 54 (27.4%) had favorable outcomes. Regression analysis showed that higher p-Tau levels correlated with unfavorable neurological outcomes. The levels of p-Tau were significantly correlated with DBP and GWR. For p-Tau to differentiate between neurological outcomes, an optimal cutoff of 456 pg/mL yielded an area under the receiver operating characteristic curve of 0.71. Combining p-Tau, GWR, and DBP improved predictive accuracy (area under the receiver operating characteristic curve = 0.80 vs. 0.71, p = 0.008). CONCLUSIONS: Plasma p-Tau levels measured within 24 h following ROSC, particularly when combined with GWR and DBP, may serve as a promising biomarker of neurological outcomes in CA survivors, with higher levels predicting unfavorable outcomes.
RESUMEN
BACKGROUND: Imipenem/relebactam (IMR) was approved for patient use in Taiwan in 2023. We evaluated the in vitro susceptibility of recent Gram-negative pathogens collected in Taiwan hospitals to IMR and comparators with a focus on carbapenem-resistant and KPC-carrying non-Morganellaceae Enterobacterales (NME), and carbapenem-resistant Pseudomonas aeruginosa (CRPA). METHODS: From 2018 to 2021, eight hospitals in Taiwan each collected up to 250 consecutive, aerobic or facultative, Gram-negative pathogens per year from patients with bloodstream, intraabdominal, lower respiratory tract, and urinary tract infections. MICs were determined using Clinical Laboratory Standards Institute (CLSI) broth microdilution. Most isolates that were IMR-, imipenem-, or ceftolozane/tazobactam-nonsusceptible were screened for ß-lactamase genes by PCR or whole-genome sequencing. RESULTS: Ninety-eight percent of NME (n = 5063) and 94% of P. aeruginosa (n = 1518) isolates were IMR-susceptible. Percent susceptible values for non-carbapenem ß-lactam comparators, including piperacillin/tazobactam, were 68-79% for NME isolates, while percent susceptible values for all ß-lactam comparators, including meropenem, were 73-81% for P. aeruginosa. IMR retained activity against 93% of multidrug-resistant (MDR) NME and 70% of MDR P. aeruginosa. Sixty-five percent of carbapenem-resistant NME and 81% of KPC-positive NME (n = 80) were IMR-susceptible. IMR inhibited 70% of CRPA (n = 287). Fifty percent of IMR-nonsusceptible NME tested for ß-lactamase carriage had an MBL or OXA-48-like enzyme, whereas most (95%) IMR-nonsusceptible P. aeruginosa examined did not carry acquired ß-lactamase genes. CONCLUSION: Based on our in vitro data, IMR may be a useful option for the treatment of hospitalized patients in Taiwan with infections caused by common Gram-negative pathogens, including carbapenem-resistant NME, KPC-positive NME, and CRPA.
Asunto(s)
Antibacterianos , Compuestos de Azabiciclo , Imipenem , Humanos , Taiwán , Antibacterianos/farmacología , Imipenem/farmacología , Carbapenémicos/farmacología , Tazobactam , Pseudomonas aeruginosa/genética , beta-Lactamas , beta-Lactamasas/genética , Pruebas de Sensibilidad MicrobianaRESUMEN
Background and Objectives: Labor epidural analgesia can be maintained through programmed intermittent epidural bolus (PIEB), continuous epidural infusion (CEI), or patient-controlled epidural analgesia (PCEA). Our department changed from CEI+PCEA to PIEB+PCEA as the maintenance method. The higher hourly dose setting in the current regimen brought to our concern that side effects would increase with proportional staff workloads. This study aimed to investigate the validity of our proposal that PIEB+PCEA may function as a feasible tool in reducing the amount of work in the obstetrics anesthesia units. Materials and methods: This 2-year retrospective review included parturients with vaginal deliveries under epidural analgesia. We compared the staff burden before and after the switch from CEI (6 mL/h, PCEA 6 mL lockout 15 min, group A) to PIEB (8 mL/h, PCEA 8 mL lockout 10 min, group B). The primary outcome was the difference of proportion of parturients requiring unscheduled visits between groups. Side effects and labor and neonatal outcomes were compared. Results: Of the 694 parturients analyzed, the proportion of those requiring unscheduled visits were significantly reduced in group B (20.8% vs. 27.7%, chi-square test, p = 0.033). The multivariate logistic regression showed that PIEB was associated with fewer unscheduled visits than CEI (OR = 0.53, 95% CI [0.36-0.80], p < 0.01). Group B exhibited a significantly lower incidence of asymmetric blockade, as well as motor blockade. In nulliparous subjects, obstetric anal sphincter injury occurred less frequently when PIEB+PCEA was used. Significantly more multiparous women experienced vacuum extraction delivery in group B than in group A, and they had a longer second stage of labor. Conclusions: The PIEB+PCEA protocol in our study reduced workloads in labor epidural analgesia as compared to CEI+PCEA, despite that a higher dose of analgesics was administered. Future studies are warranted to investigate the effect of manipulating the PIEB settings on the labor outcomes.
Asunto(s)
Analgesia Epidural , Analgesia Obstétrica , Humanos , Femenino , Embarazo , Adulto , Estudios Retrospectivos , Analgesia Epidural/métodos , Analgesia Epidural/estadística & datos numéricos , Analgesia Obstétrica/métodos , Analgesia Obstétrica/estadística & datos numéricos , Analgesia Controlada por el Paciente/métodos , Analgesia Controlada por el Paciente/estadística & datos numéricos , Carga de Trabajo/estadística & datos numéricos , Trabajo de Parto/efectos de los fármacos , Trabajo de Parto/fisiologíaRESUMEN
BACKGROUND AND AIMS: HCV-specific T cells are few and exhausted in patients with chronic hepatitis C (CHC). Whether these T cells are responsible for the liver damage and fibrosis is still debated. However, cluster of differentiation 38-positive (CD38+ ) human leukocyte antigen DR-positive (HLA-DR+ ) CD8+ T cells are regarded as bystander CD8+ T cells that cause liver injury in acute hepatitis. We propose that these innate CD8+ T cells play a pathogenic role in CHC. METHODS: Lymphocytes from peripheral blood were obtained from 108 patients with CHC and 43 healthy subjects. Immunophenotyping, functional assays, T-cell receptor (TCR) repertoire, and cytotoxic assay of CD38+ HLA-DR+ CD8+ T cells were studied. RESULTS: The percentage of CD38+ HLA-DR+ CD8+ T cells increased significantly in patients with CHC. These cells expressed higher levels of effector memory and proinflammatory chemokine molecules and showed higher interferon-γ production than CD38- HLA-DR- CD8 T cells. They were largely composed of non-HCV-specific CD8+ T cells as assessed by HLA-A2-restricted pentamers and next-generation sequencing analysis of the TCR repertoire. In addition, these CD38+ HLA-DR+ CD8+ T cells had strong cytotoxicity, which could be inhibited by anti-DNAX accessory molecule 1, anti-NKG2 family member D, and anti-natural killer NKp30 antibodies. Lastly, the percentage of CD38+ HLA-DR+ CD8+ T cells was significantly associated with liver injury and fibrosis and decreased significantly along with serum alanine aminotransferase normalization after successful direct-acting antiviral treatment. CONCLUSIONS: The TCR-independent, cytokine-responsive bystander CD38+ HLA-DR+ CD8+ T cells are strongly cytotoxic and play a pathogenic role in patients with CHC.
Asunto(s)
Linfocitos T CD8-positivos , Hepatitis C Crónica , ADP-Ribosil Ciclasa 1/inmunología , Antivirales , Antígenos HLA-DR , Humanos , Glicoproteínas de Membrana/inmunología , Receptores de Antígenos de Linfocitos TRESUMEN
Background: Cerebral computed tomography (CT) and various severity scoring systems have been developed for the early prediction of the neurological outcomes of cardiac arrest survivors. However, few studies have combined these approaches. Therefore, we evaluated the value of the combination of cerebral CT and severity score for neuroprognostication. Methods: This single-center, retrospective observational study included consecutive patients surviving nontraumatic cardiac arrest (January 2016 and December 2020). Gray-to-white ratio (GWR), third and fourth ventricle characteristics, and medial temporal lobe atrophy scores were evaluated on noncontrast cerebral CT. Simplified cardiac arrest hospital prognosis (sCAHP) score was calculated for severity assessment. The associations between the CT characteristics, sCAHP score and neurological outcomes were analyzed. Results: This study enrolled 559 patients. Of them, 194 (34.7%) were discharged with favorable neurological outcomes. Patients with favorable neurological outcome had a higher GWR (1.37 vs 1.25, p < 0.001), area of fourth ventricle (461 vs 413 mm 2 , p < 0.001), anteroposterior diameter of fourth ventricle (0.95 vs 0.86 cm , p < 0.001) and a lower sCAHP score (146 vs 190, p < 0.001) than those with poor recovery. Patients with higher sCAHP score had lower GWR (p trend < 0.001), area of fourth ventricle (p trend = 0.019) and anteroposterior diameter of fourth ventricle (p trend = 0.014). The predictive ability by using area under receiver operating characteristic curve (AUC) for the combination of sCAHP score and GWR was significantly higher than that calculated for sCAHP (0.86 vs 0.76, p < 0.001) or GWR (0.86 vs 0.81, p = 0.001) alone. Conclusions: The combination of GWR and sCAHP score can be used to effectively predict the neurological outcomes of cardiac arrest survivors and thus ensure timely intervention for those at high risk of poor recovery.
RESUMEN
Si/SiGe stacked multilayers are key elements in fabrication of gate-all-around (GAA) structures and improvement of electrical properties, with the evolution of the Si/SiGe interfaces playing a crucial role. In this work, a model is developed based on the simplified bond hyperpolarizability model (SBHM) to analysis the anisotropic reflective second harmonic generation (Ani-RSHG) on a three-period stacked Si/Si1-xGexmultilayer, which builds on Si(100) diamond structures. TheC4vsymmetry of the Si(100) structure enables the second harmonic generation (SHG) contribution from the bonds to be simplified and the effective hyperpolarizabilities of the interfacial and bulk sources to be obtained. The effective interface dipolar and bulk quadrupolar SHG hyperpolarizabilities in the Si1-xGexsample with various Ge concentration profiles are modeled by interpreting the concentration of a component element as the probability of the element occupying an atomic site. On the basis of the developed model, the Ani-RSHG spectra of the as-grown samples with various Ge ratios for each layer and the samples annealed at 850 °C and 950 °C are analyzed to inspect the change in Ge distribution and its gradient in depth. The ani-RSHG analysis on as-grown samples showed difference in Ge distribution in samples with the multi Si/SiGe structure, which is not well observed in synchrotron x-ray diffraction (XRD) spectra. For the annealed samples, the response to changes in Ge concentration and its gradient in depth reveal the Si/Si1-xGexinterface intermixing. Results of high-angle annular dark-field scanning transmission electron microscopy and energy dispersive x-ray spectroscopy agree well with the Ani-RSHG with SBHM findings. Compared with the Raman and synchrotron XRD spectra, the Ani-RSHG with SBHM simulation result demonstrates much better response to changes in compositions of the Si/Si1-xGexstacked multilayered structures, verifying the potential for characterizing the concentration distribution in stacked multilayered thin films for GAA structures.
RESUMEN
AIM: Data on the geoepidemiology and outcomes of primary biliary cholangitis (PBC) in Asia are limited; thus, we aimed to collect and assess this information for Taiwan. METHODS: A nationwide population-based cohort study was undertaken using data from the Taiwan National Health Insurance Research Database. Primary biliary cholangitis was defined by the International Classification of Diseases, Ninth Revision, Clinical Modification code 571.6 based on alkaline phosphatase and antimitochondrial antibody measurements and ursodeoxycholic acid treatment. RESULTS: During 2002-2015, 2737 patients (2137 female patients; mean age, 57.78 years) had PBC. The average annual age- and sex-adjusted prevalence and incidence rates of PBC were 8.092/105 and 1.148/105 , respectively. Prevalent cases peaked in patients aged 50-59 years; the female-to-male ratio was 4.21. Annual prevalence rates increased with time (average percentage change, 12.03%; p < 0.0001). The annual incidence rates decreased with time (-7.39%; p = 0.000011) in female patients (-8.94%; p = 0.000003) but remained steady in male patients. Female-to-male and northern-to-southern relative risks of PBC incidence rates ranged from 2.2675 to 4.3318 and from 1.5707 to 3.1725, respectively. The 14-year hepatocellular carcinoma (HCC) cumulative incidence was 9.11%, and the mortality rate was 32.44%; the cumulative incidences of dyslipidemia, thyroid disease, and extrahepatic cancers were 65.13%, 24.40%, and 12.79%, respectively. Higher cumulative incidences of HCC (p = 0.0064) and mortality (p < 0.0001) were noted in male than female PBC patients; southern Taiwan PBC patients had higher cumulative incidences of mortality (p < 0.0001) than their northern counterparts. CONCLUSION: In Taiwan, decreasing trends in incidence rates and the female-to-male ratio of PBC patients and specific sex and geographic impacts on the incidence rates and outcomes of PBC demand further investigation.
RESUMEN
Lack of trust in biomedical research, government, and health care systems, especially among racial/ethnic minorities and under-resourced communities, is a longstanding issue rooted in social injustice. The COVID-19 pandemic has further highlighted existing health and socioeconomic inequities and increased the urgency for solutions to provide access to timely, culturally, and linguistically appropriate evidence-based information about COVID-19; and ultimately to promote vaccine uptake. California's statewide alliance STOP COVID-19 CA (comprising eleven sites), leverages long standing community partnerships to better understand concerns, misinformation, and address racial/ethnic inequities in vaccine hesitancy and uptake. Using data from the California CEAL Communication Working Group, we demonstrate the wide range of strategies, communication methods, languages, and trusted messengers that have been effective in reaching diverse communities across the state. We also showcase challenges and lessons learned, such as the importance of including trusted community partners to share information or provide vaccines. These approaches, rooted in community engagement, are crucial for addressing inequities and responding to future public health emergencies.
Asunto(s)
COVID-19 , Vacilación a la Vacunación , Humanos , Pandemias , COVID-19/prevención & control , Grupos Raciales , CaliforniaRESUMEN
INTRODUCTION: Adequate bowel preparation is key to a successful colonoscopy, which is necessary for detecting adenomas and preventing colorectal cancer. We developed an artificial intelligence (AI) platform using a convolutional neural network (CNN) model (AI-CNN model) to evaluate the quality of bowel preparation before colonoscopy. METHODS: This was a colonoscopist-blinded, randomized study. Enrolled patients were randomized into an experimental group, in which our AI-CNN model was used to evaluate the quality of bowel preparation (AI-CNN group), or a control group, which performed self-evaluation per routine practice (control group). The primary outcome was the consistency (homogeneity) between the results of the 2 methods. The secondary outcomes included the quality of bowel preparation according to the Boston Bowel Preparation Scale (BBPS), polyp detection rate, and adenoma detection rate. RESULTS: A total of 1,434 patients were enrolled (AI-CNN, n = 730; control, n = 704). No significant difference was observed between the evaluation results ("pass" or "not pass") of the groups in the adequacy of bowel preparation as represented by BBPS scores. The mean BBPS scores, polyp detection rate, and adenoma detection rate were similar between the groups. These results indicated that the AI-CNN model and routine practice were generally consistent in the evaluation of bowel preparation quality. However, the mean BBPS score of patients with "pass" results were significantly higher in the AI-CNN group than in the control group, indicating that the AI-CNN model may further improve the quality of bowel preparation in patients exhibiting adequate bowel preparation. DISCUSSION: The novel AI-CNN model, which demonstrated comparable outcomes to the routine practice, may serve as an alternative approach for evaluating bowel preparation quality before colonoscopy.
Asunto(s)
Adenoma , COVID-19 , Pólipos del Colon , Adenoma/diagnóstico , Inteligencia Artificial , Catárticos , Pólipos del Colon/diagnóstico por imagen , Colonoscopía/métodos , Humanos , Redes Neurales de la Computación , Estudios ProspectivosRESUMEN
OBJECTIVES: To evaluate whether the recommended observation period of 7 days for cardiac arrest survivors is sufficient for conscious recovery and to identify the variables associated with eventual neurologic recovery among patients with delayed awakening. DESIGN: A retrospective cohort study. SETTING: A single tertiary medical center. PATIENTS: Five-hundred twenty-nine nontraumatic adult cardiac arrest survivors with prearrest favorable neurologic function (Cerebral Performance Category 1-2) who survived to hospital discharge during 2011-2019. INTERVENTIONS: The enrolled patients were classified into favorable (Cerebral Performance Category 1-2) and poor (Cerebral Performance Category 3-4) neurologic recovery according to their neurologic function at hospital discharge. Among patients with favorable neurologic recovery, those who recovered within 7 days were assigned to the early recovery group or after 7 days as the late recovery group. MEASUREMENTS AND MAIN RESULTS: There were 395 patients exhibiting favorable neurologic recovery (n = 357 in the early group, n = 38 in late group) and 134 patients exhibiting poor neurologic recovery (poor recovery group). Among patients who remained unconscious on day 7, delayed awakening was associated with male sex (odds ratio [OR], 3.905; 95% CI, 1.153-13.221), prehospital return of spontaneous circulation (OR, 7.628; 95% CI, 2.084-27.922), therapeutic hypothermia (OR, 4.320; 95% CI, 1.624-11.488), and extracorporeal cardiopulmonary resuscitation (OR, 4.508; 95% CI, 1.414-14.371). Being transferred from another hospital, however, was less likely to be associated with delayed awakening (OR, 0.061; 95% CI, 0.009-0.431). The median duration for patients to regain clear consciousness in the late recovery group was 12.12 days. No patient who recovered consciousness had an unfavorable electroencephalography pattern, however, in patients with poor recovery, the 7-day electroencephalography showed 45 patients with generalized suppression (33.6%), two with burst suppression (1.5%), 14 with seizure/epileptic discharge (10.5%), and one with status epilepticus (0.7%). CONCLUSIONS: Up to 9.6% of cardiac arrest patients with favorable outcomes recover consciousness after the recommended 7 days of observation, indicating the observation time of 7 days seems justified but longer duration may be needed. The results of the culturally and clinically isolated population may limit the application to other population.