Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 235
Filtrar
1.
J Intensive Care Med ; : 8850666241268390, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39094594

RESUMEN

BACKGROUND: Acute kidney injury (AKI) is common in sepsis and a urine output <0.5 mL/kg/h associated with increased mortality is incorporated into AKI diagnosis. We aimed to identify the urine-output threshold associated with increased AKI incidence and hypothesized that a higher urine output than a specified threshold, which differs from the predominantly used 0.5 mL/kg/h threshold, would be associated with an increased AKI incidence. METHODS: This was a post-hoc analysis of a nationwide prospective observational study. This study included adult patients newly diagnosed with sepsis and requiring intensive care. Urine output on the day of sepsis diagnosis was categorized as low, moderate, or high (<0.5, 0.5-1.0, and >1.0 mL/kg/h, respectively), and we compared AKI incidence, renal replacement therapy (RRT) requirement, and 28-day survival by category. Estimated probabilities for these outcomes were also compared after adjusting for patient background and hourly fluid administration. RESULTS: Among 172 eligible patients, AKI occurred in 46.3%, 48.3%, and 53.1% of those with high, moderate, and low urine output, respectively. The probability of AKI was lower in patients with high urine output than in those with low output (43.6% vs 56.5%; P = .028), whereas RRT requirement was lower in patients with high and moderate urine output (11.7% and 12.8% vs 49.1%; P < .001). Patients with low urine output demonstrated significantly lower survival (87.7% vs 82.8% and 67.8%; P = .018). Cubic spline curves for AKI, RRT, and survival prediction indicated different urine-output thresholds, including <1.2 to 1.3 mL/kg/h for AKI and <0.6 to 0.8 mL/kg/h for RRT and mortality risk. CONCLUSIONS: Urine output >1.0 mL/kg/h on the day of sepsis diagnosis was associated with lower AKI incidence. The urine-output threshold was higher for developing AKI than for RRT requirement or mortality.

2.
Int J Surg ; 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39116449

RESUMEN

BACKGROUND: Perforated peptic ulcer (PPU) causes peritonitis and requires surgery based on disease severity. This study aimed to develop and validate a severity scale for PPU with generalized peritonitis. MATERIALS AND METHODS: This retrospective cohort study used a nationwide multi-center surgical database (2013-2020). Patients aged >15 years who underwent surgery for PPU with generalized peritonitis were included and categorized into the derivation (2013-2018) and two validation (2019 and 2020) cohorts. Possible severity predictors were selected via a literature review, and Lasso models were developed to predict severe postoperative adverse events with 2000 bootstrapping. Final variables for the scoring system were determined based on inclusion frequency (≥90%) in the Lasso models. Discrimination and accuracy were evaluated using c-statistics and calibration plots. Cutoff values for minimal postoperative adverse events were examined using negative predictive values. RESULTS: Among 12,513 patients included (1,202 underwent laparoscopic surgery), 533 (5.9%), 138 (7.6%), and 117 (6.9%) in the derivation and two validation cohorts experienced postoperative adverse events. Age, dyspnea at rest, preoperative sepsis, III/IV/V of American Society of Anesthesiologists physical status, and albumin and creatinine were selected for the final model. A 0-11 scoring system was developed with c-statistics of 0.812-0.819. Cutoff value was determined as 5, which predicted <3% probability of postoperative adverse events regardless of type of surgery. CONCLUSIONS: A score of <5 predicts minimal risks for postoperative adverse events and therefore would be clinically useful to determine type of surgery. Further studies are needed to validate the score.

3.
IUCrdata ; 9(Pt 6): x240615, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38974848

RESUMEN

The title compound, C15H12BN3, is a type of di-aza-borinane featuring substitution at 1, 2, and 3 positions in the nitro-gen-boron six-membered heterocycle. It is comprised of two almost planar units, the pyridyl ring and the Bdan (dan = 1,8-di-aminona-phtho) group, which subtend a dihedral angle of 24.57 (5)°. In the crystal, the mol-ecules are linked into R 4 4(28) hydrogen-bonding networks around the fourfold inversion axis, giving cyclic tetra-mers. The mol-ecules form columnar stacks along the c axis.

4.
J Mol Biol ; 436(16): 168666, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38880378

RESUMEN

Heliorhodopsin (HeR) is a new rhodopsin family discovered in 2018 through functional metagenomic analysis. Similar to microbial rhodopsins, HeR has an all-trans retinal chromophore, and its photoisomerization to the 13-cis form triggers a relatively slow photocycle with sequential intermediate states (K, M, and O intermediates). The O intermediate has a relatively long lifetime and is a putative active state for transferring signals or regulating enzymatic reactions. Although the first discovered HeR, 48C12, was found in bacteria and the second HeR (TaHeR) was found in archaea, their key amino acid residues and molecular architectures have been recognized to be well conserved. Nevertheless, the rise and decay kinetics of the O intermediate are faster in 48C12 than in TaHeR. Here, using a new infrared spectroscopic technique with quantum cascade lasers, we clarified that the hydrogen bond between transmembrane helices (TM) 3 and 4 is essential for the altered O kinetics (Ser112 and Asn138 in 48C12). Interconverting mutants of 48C12 and TaHeR clearly revealed that the hydrogen bond is important for regulating the dynamics of the O intermediate. Overall, our study sheds light on the importance of the hydrogen bond between TM3 and TM4 in heliorhodopsins, similar to the DC gate in channelrhodopsins.


Asunto(s)
Enlace de Hidrógeno , Cinética , Rodopsinas Microbianas/química , Rodopsinas Microbianas/metabolismo , Rodopsinas Microbianas/genética , Serina/química , Serina/metabolismo , Asparagina/química , Asparagina/metabolismo , Modelos Moleculares , Conformación Proteica
5.
Pediatr Int ; 66(1): e15767, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38924178

RESUMEN

BACKGROUND: Twin pregnancies are associated with a high risk of perinatal mortality and morbidity. Late preterm or early term delivery is frequently performed to avoid unexpected fetal death in uncomplicated twin pregnancies. Nonetheless, delivery before full term is associated with neonatal respiratory complications. This study aimed to evaluate perinatal respiratory complications in twins delivered between 36 and 38 weeks of gestation. METHODS: A retrospective cohort study was conducted on twins delivered between 36 and 38 weeks of gestation from January 2008 to June 2020. The primary outcomes were the incidence of composite neonatal respiratory morbidity, which included respiratory distress syndrome, transient tachypnea of the newborn, meconium aspiration syndrome, mechanical ventilation or continuous positive airway pressure according to gestational age at delivery, and chorionicity. The relationship between gestational age at delivery and composite neonatal respiratory morbidity was evaluated using multivariate logistic regression analysis adjusted for potential confounders. RESULTS: This study included 1608 twins (614 monochorionic diamniotic twins, 994 dichorionic diamniotic twins). At 36, 37, and 38 weeks of gestation, the frequencies of composite neonatal respiratory morbidity were 19.4%, 10.7%, and 9.2% in dichorionic diamniotic twins and 13.6%, 8.7%, and 9.4% in monochorionic diamniotic twins, respectively. In dichorionic diamniotic twins, the composite neonatal respiratory morbidity rate was higher for twins delivered at 36 weeks of gestation than for those delivered at 37 weeks. No significant differences between monochorionic diamniotic twins were detected. CONCLUSIONS: In uncomplicated dichorionic diamniotic twin pregnancies, delivery should be considered after 37 weeks of gestation to reduce neonatal respiratory complications.


Asunto(s)
Edad Gestacional , Embarazo Gemelar , Síndrome de Dificultad Respiratoria del Recién Nacido , Humanos , Recién Nacido , Femenino , Estudios Retrospectivos , Embarazo , Síndrome de Dificultad Respiratoria del Recién Nacido/epidemiología , Síndrome de Dificultad Respiratoria del Recién Nacido/etiología , Masculino , Taquipnea Transitoria del Recién Nacido/epidemiología , Síndrome de Aspiración de Meconio/epidemiología , Incidencia , Respiración Artificial , Presión de las Vías Aéreas Positiva Contínua , Gemelos
6.
Viruses ; 16(6)2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38932120

RESUMEN

A gene delivery system utilizing lentiviral vectors (LVs) requires high transduction efficiency for successful application in human gene therapy. Pseudotyping allows viral tropism to be expanded, widening the usage of LVs. While vesicular stomatitis virus G (VSV-G) single-pseudotyped LVs are commonly used, dual-pseudotyping is less frequently employed because of its increased complexity. In this study, we examined the potential of phenotypically mixed heterologous dual-pseudotyped LVs with VSV-G and Sendai virus hemagglutinin-neuraminidase (SeV-HN) glycoproteins, termed V/HN-LV. Our findings demonstrated the significantly improved transduction efficiency of V/HN-LV in various cell lines of mice, cynomolgus monkeys, and humans compared with LV pseudotyped with VSV-G alone. Notably, V/HN-LV showed higher transduction efficiency in human cells, including hematopoietic stem cells. The efficient incorporation of wild-type SeV-HN into V/HN-LV depended on VSV-G. SeV-HN removed sialic acid from VSV-G, and the desialylation of VSV-G increased V/HN-LV infectivity. Furthermore, V/HN-LV acquired the ability to recognize sialic acid, particularly N-acetylneuraminic acid on the host cell, enhancing LV infectivity. Overall, VSV-G and SeV-HN synergistically improve LV transduction efficiency and broaden its tropism, indicating their potential use in gene delivery.


Asunto(s)
Vectores Genéticos , Proteína HN , Lentivirus , Virus Sendai , Transducción Genética , Proteínas del Envoltorio Viral , Animales , Humanos , Vectores Genéticos/genética , Lentivirus/genética , Virus Sendai/genética , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/metabolismo , Ratones , Proteína HN/genética , Proteína HN/metabolismo , Línea Celular , Macaca fascicularis , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Tropismo Viral , Células HEK293 , Técnicas de Transferencia de Gen , Terapia Genética/métodos
7.
World J Emerg Surg ; 19(1): 19, 2024 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-38822409

RESUMEN

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been used to control massive hemorrhages. Although there is no consensus on the efficacy of REBOA, it remains an option as a bridging therapy in non-trauma centers where trauma surgeons are not available. To better understand the current landscape of REBOA application, we examined changes in its usage, target population, and treatment outcomes in Japan, where immediate hemostasis procedures sometimes cannot be performed. METHODS: This retrospective observational study used the Japan Trauma Data Bank data. All cases in which REBOA was performed between January 2004 and December 2021 were included. The primary outcome was the in-hospital mortality rate. We analyzed mortality trends over time according to the number of cases, number of centers, severity of injury, and overall and subgroup mortality associated with REBOA usage. We performed a logistic analysis of mortality trends over time, adjusting for probability of survival based on the trauma and injury severity score. RESULTS: Overall, 2557 patients were treated with REBOA and were deemed eligible for inclusion. The median age of the participants was 55 years, and male patients constituted 65.3% of the study population. Blunt trauma accounted for approximately 93.0% of the cases. The number of cases and facilities that used REBOA increased until 2019. While the injury severity score and revised trauma score did not change throughout the observation period, the hospital mortality rate decreased from 91.3 to 50.9%. The REBOA group without severe head or spine injuries showed greater improvement in mortality than the all-patient group using REBOA and all-trauma patient group. The greatest improvement in mortality was observed in patients with systolic blood pressure ≥ 80 mmHg. The adjusted odds ratios for hospital mortality steadily declined, even after adjusting for the probability of survival. CONCLUSIONS: While there was no significant change in patient severity, mortality of patients treated with REBOA decreased over time. Further research is required to determine the reasons for these improvements in trauma care.


Asunto(s)
Oclusión con Balón , Procedimientos Endovasculares , Puntaje de Gravedad del Traumatismo , Resucitación , Humanos , Oclusión con Balón/métodos , Japón , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Resucitación/métodos , Adulto , Procedimientos Endovasculares/métodos , Anciano , Mortalidad Hospitalaria , Aorta/cirugía , Aorta/lesiones , Heridas y Lesiones/terapia , Heridas y Lesiones/mortalidad , Hemorragia/terapia , Hemorragia/mortalidad
8.
J Am Heart Assoc ; 13(12): e034971, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38842281

RESUMEN

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is an option for refractory cardiac arrest, and immediate initiation after indication is recommended. However, the practical goals of ECPR preparation (such as the door-to-needle time) remain unclear. This study aimed to elucidate the association between the door-to-needle time and neurological outcomes of out-of-hospital cardiac arrest. METHODS AND RESULTS: This is a post hoc analysis of a nationwide multicenter study on out-of-hospital cardiac arrest treated with ECPR at 36 institutions between 2013 and 2018 (SAVE-J [Study of Advanced Cardiac Life Support for Ventricular Fibrillation with Extracorporeal Circulation in Japan] II study). Adult patients without hypothermia (≥32 °C) in whom circulation was not returned at ECPR initiation were included. The probability of favorable neurological function at 30 days (defined as Cerebral Performance Category ≤2) was estimated using a generalized estimating equations model, in which institutional, patient, and treatment characteristics were adjusted. Estimated probabilities were then calculated according to the door-to-needle time with 3-minute increments, and a clinical threshold was assumed. Among 1298 patients eligible for this study, 136 (10.6%) had favorable neurological function. The estimated probability of favorable outcomes was highest in patients with 1 to 3 minutes of door-to-needle time (12.9% [11.4%-14.3%]) and remained at 9% to 10% until 27 to 30 minutes. Then, the probability dropped gradually with each 3-minute delay. A 30-minute threshold was assumed, and shorter door-to-extracorporeal membrane oxygenation/low-flow time and fewer adverse events related to cannulation were observed in patients with door-to-needle time <30 minutes. CONCLUSIONS: The probability of favorable functions after out-of-hospital cardiac arrest decreased as the door-to-needle time for ECPR was prolonged, with a rapid decline after 27 to 30 minutes. REGISTRATION: URL: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000041577; Unique identifier: UMIN000036490.


Asunto(s)
Reanimación Cardiopulmonar , Oxigenación por Membrana Extracorpórea , Paro Cardíaco Extrahospitalario , Tiempo de Tratamiento , Humanos , Paro Cardíaco Extrahospitalario/terapia , Paro Cardíaco Extrahospitalario/fisiopatología , Paro Cardíaco Extrahospitalario/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Japón/epidemiología , Oxigenación por Membrana Extracorpórea/métodos , Oxigenación por Membrana Extracorpórea/efectos adversos , Reanimación Cardiopulmonar/métodos , Anciano , Resultado del Tratamiento , Factores de Tiempo
9.
Sci Immunol ; 9(95): eade3814, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38787963

RESUMEN

Patients with heart failure (HF) often experience repeated acute decompensation and develop comorbidities such as chronic kidney disease and frailty syndrome. Although this suggests pathological interaction among comorbidities, the mechanisms linking them are poorly understood. Here, we identified alterations in hematopoietic stem cells (HSCs) as a critical driver of recurrent HF and associated comorbidities. Bone marrow transplantation from HF-experienced mice resulted in spontaneous cardiac dysfunction and fibrosis in recipient mice, as well as increased vulnerability to kidney and skeletal muscle insults. HF enhanced the capacity of HSCs to generate proinflammatory macrophages. In HF mice, global chromatin accessibility analysis and single-cell RNA-seq showed that transforming growth factor-ß (TGF-ß) signaling was suppressed in HSCs, which corresponded with repressed sympathetic nervous activity in bone marrow. Transplantation of bone marrow from mice in which TGF-ß signaling was inhibited similarly exacerbated cardiac dysfunction. Collectively, these results suggest that cardiac stress modulates the epigenome of HSCs, which in turn alters their capacity to generate cardiac macrophage subpopulations. This change in HSCs may be a common driver of repeated HF events and comorbidity by serving as a key carrier of "stress memory."


Asunto(s)
Insuficiencia Cardíaca , Inmunidad Innata , Memoria Inmunológica , Ratones Endogámicos C57BL , Animales , Insuficiencia Cardíaca/inmunología , Ratones , Masculino , Multimorbilidad , Factor de Crecimiento Transformador beta/metabolismo , Células Madre Hematopoyéticas/inmunología , Transducción de Señal/inmunología , Macrófagos/inmunología , Inmunidad Entrenada
10.
J Vis Exp ; (207)2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38758020

RESUMEN

This corrects the article 10.3791/66266.

11.
Artículo en Inglés | MEDLINE | ID: mdl-38780783

RESUMEN

PURPOSE: While follow-up CT and prophylactic embolization with angiography are often conducted during non-operative management (NOM) for BLSI, particularly in a high-grade injury, the utility of early repeated CT for preventing unexpected hemorrhage remains unclear. This study aimed to elucidate whether early follow-up computerized tomography (CT) within 7 days after admission would decrease unexpected hemostatic procedures on pediatric blunt liver and spleen injury (BLSI). METHODS: A post-hoc analysis of a multicenter observational cohort study on pediatric patients with BLSI (2008-2019) was conducted on those who underwent NOM, in whom the timing of follow-up CT were decided by treating physicians. The incidence of unexpected hemostatic procedure (laparotomy and/or emergency angiography for ruptured pseudoaneurysm) and complications related to BLSI were compared between patients with and without early follow-up CT within 7 days. Inverse probability weighting with propensity scores adjusted patient demographics, comorbidities, mechanism and severity of injury, initial resuscitation, and institutional characteristics. RESULTS: Among 1320 included patients, 552 underwent early follow-up CT. Approximately 25% of patients underwent angiography on the day of admission. The incidence of unexpected hemostasis was similar between patients with and without early repeat CT (8 [1.4%] vs. 6 [0.8%]; adjusted OR, 1.44 [0.62-3.34]; p = 0.40). Patients with repeat CT scans more frequently underwent multiple angiographies (OR, 2.79 [1.32-5.88]) and had more complications related to BLSI, particularly bile leak (OR, 1.73 [1.04-2.87]). CONCLUSION: Follow-up CT scans within 7 days was not associated with reduced unexpected hemostasis in NOM for pediatric BLSI.

12.
Sensors (Basel) ; 24(10)2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38794075

RESUMEN

The recent rapid growth in Internet of Things (IoT) technologies is enriching our daily lives but significant information security risks in IoT fields have become apparent. In fact, there have been large-scale botnet attacks that exploit undiscovered vulnerabilities, known as zero-day attacks. Several intrusion detection methods based on network traffic monitoring have been proposed to address this issue. These methods employ federated learning to share learned attack information among multiple IoT networks, aiming to improve collective detection capabilities against attacks including zero-day attacks. Although their ability to detect zero-day attacks with high precision has been confirmed, challenges such as autonomous labeling of attacks from traffic information and attack information sharing between different device types still remain. To resolve the issues, this paper proposes IDAC, a novel intrusion detection method with autonomous attack candidate labeling and federated learning-based attack candidate sharing. The labeling of attack candidates in IDAC is executed using information autonomously extracted from traffic information, and the labeling can also be applied to zero-day attacks. The federated learning-based attack candidate sharing enables candidate aggregation from multiple networks, and it executes attack determination based on the aggregated similar candidates. Performance evaluations demonstrated that IDS with IDAC within networks based on attack candidates is feasible and achieved comparable detection performance against multiple attacks including zero-day attacks compared to the existing methods while suppressing false positives in the extraction of attack candidates. In addition, the sharing of autonomously extracted attack candidates from multiple networks improves both detection performance and the required time for attack detection.

13.
Nutrients ; 16(10)2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38794690

RESUMEN

BACKGROUND: The utility of using indirect calorimetry (IC) to estimate energy needs and methods for its application to this purpose remain unclear. This systematic review investigated whether using IC to estimate energy expenditure in critically ill patients is more meaningful for improving survival than other estimation methods. METHODS: Comprehensive searches were conducted in MEDLINE using PubMed, Cochrane Central Register of Controlled Trials, and Igaku-Chuo-Zasshi up to March 2023. RESULTS: Nine RCTs involving 1178 patients were included in the meta-analysis. The evidence obtained suggested that energy delivery by IC improved short-term mortality (risk ratio, 0.86; 95% confidence interval [CI], 0.70 to 1.06). However, the use of IC did not appear to affect the length of ICU stay (mean difference [MD], 0.86; 95% CI, -0.98 to 2.70) or the duration of mechanical ventilation (MD, 0.66; 95% CI, -0.39 to 1.72). Post hoc analyses using short-term mortality as the outcome found no significant difference by target calories in resting energy expenditure, whereas more frequent IC estimates were associated with lower short-term mortality and were more effective in mechanically ventilated patients. CONCLUSIONS: This updated meta-analysis revealed that the use of IC may improve short-term mortality in patients with critical illness and did not increase adverse events.


Asunto(s)
Calorimetría Indirecta , Enfermedad Crítica , Metabolismo Energético , Enfermedad Crítica/terapia , Humanos , Respiración Artificial , Ingestión de Energía , Tiempo de Internación , Unidades de Cuidados Intensivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Apoyo Nutricional/métodos
14.
BMC Musculoskelet Disord ; 25(1): 314, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38654188

RESUMEN

BACKGROUND: The role of lactate level in selecting the timing of definitive surgery for isolated extremity fracture remains unclear. Therefore, we aimed to elucidate the use of preoperative lactate level for predicting early postoperative complications. METHODS: This was a single-center retrospective observational study of patients with isolated extremity fracture who underwent orthopedic surgery. Patients who underwent lactate level assessment within 24 h prior to surgery were included. The incidence of early postoperative complications was compared between patients with a preoperative lactate level of ≥ 2 and < 2 mmol/L. Moreover, subgroup analyses were performed based on the time from hospital arrival to surgery and fracture type. RESULTS: In total, 187 patients were included in the study. The incidence of postoperative complications was significantly higher in patients with a preoperative lactate level of ≥ 2 mmol/L than those with a preoperative lactate level of < 2 mmol/L. This result did not change after adjusting for age and severity. Further, a high preoperative lactate level was associated with a greater incidence of postoperative complications in patients who underwent definitive surgery within 6 h after arrival. CONCLUSION: A preoperative lactate level of ≥ 2 mmol/L was associated with a greater incidence of early postoperative complications in isolated extremity fractures. Nevertheless, this correlation was only observed among patients who underwent definitive fixation within 6 h after hospital arrival.


Asunto(s)
Fracturas Óseas , Ácido Láctico , Complicaciones Posoperatorias , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/diagnóstico , Ácido Láctico/sangre , Anciano , Adulto , Fracturas Óseas/cirugía , Fracturas Óseas/sangre , Fracturas Óseas/epidemiología , Incidencia , Factores de Tiempo , Periodo Preoperatorio , Biomarcadores/sangre
15.
Brain Res ; 1835: 148934, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38609029

RESUMEN

The membrane raft accommodates the key enzymes synthesizing amyloid ß (Aß). One of the two characteristic components of the membrane raft, cholesterol, is well known to promote the key enzymes that produce amyloid-ß (Aß) and exacerbate Alzheimer's disease (AD) pathogenesis. Given that the raft is a physicochemical platform for the sound functioning of embedded bioactive proteins, the other major lipid component sphingomyelin may also be involved in AD. Here we knocked out the sphingomyelin synthase 2 gene (SMS2) in 3xTg AD model mice by hybridization, yielding SMS2KO mice (4S mice). The novel object recognition test in 9/10-month-old 4S mice showed that cognitive impairment in 3xTg mice was alleviated by SMS2KO, though performance in the Morris water maze (MWM) was not improved. The tail suspension test detected a depressive trait in 4S mice, which may have hindered the manifestation of performance in the wet, stressful environment of MWM. In the hippocampal CA1, hyperexcitability in 3xTg was also found alleviated by SMS2KO. In the hippocampal dentate gyrus of 4S mice, the number of neurons positive with intracellular Aß or its precursor proteins, the hallmark of young 3xTg mice, is reduced to one-third, suggesting an SMS2KO-led suppression of syntheses of those peptides in the dentate gyrus. Although we previously reported that large-conductance calcium-activated potassium (BK) channels are suppressed in 3xTg mice and their recovery relates to cognitive amelioration, no changes occurred by hybridization. Sphingomyelin in the membrane raft may serve as a novel target for AD drugs.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Modelos Animales de Enfermedad , Ratones Noqueados , Ratones Transgénicos , Transferasas (Grupos de Otros Fosfatos Sustitutos) , Animales , Transferasas (Grupos de Otros Fosfatos Sustitutos)/genética , Transferasas (Grupos de Otros Fosfatos Sustitutos)/metabolismo , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/genética , Ratones , Péptidos beta-Amiloides/metabolismo , Masculino , Aprendizaje por Laberinto/fisiología , Hipocampo/metabolismo , Ratones Endogámicos C57BL
16.
Heliyon ; 10(7): e28821, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38596059

RESUMEN

The amyloid plaque is a hallmark of Alzheimer's disease. The accumulation of the amyloid precursor protein (APP) in the neuronal structure is assumed to lead to amyloid plaque formation through the excessive production of ß-amyloid protein. To study the relationship between the neuronal accumulation of APP and amyloid plaque formation, we histologically analyzed their development in the different brain regions in 3xTg-AD mice, which express Swedish mutated APP (APPSWE) in the neurons. Observation throughout the brain revealed APPSWE-positive somata in the broad regions. Quantitative model analysis showed that the somatic accumulation of APPSWE developed firstly in the hippocampus from a very early age (<1 month) and proceeded slower in the isocortex. In line with this, the hippocampus was the first region to form amyloid plaques at the age of 9-12 months, while amyloid plaques were rarely observed in the isocortex. Females had more APPSWE-positive somata and plaques than males. Furthermore, amyloid plaques were observed in the lateral septum and pontine grey, which did not contain APPSWE-positive somata but only the APPSWE-positive fibers. These results suggested that neuronal accumulation of APPSWE, both in somatodendritic and axonal domains, is closely related to the formation of amyloid plaques.

17.
Cardiovasc Intervent Radiol ; 47(4): 472-480, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38332119

RESUMEN

PURPOSE: This study aimed to elucidate whether immediate angiography within 30 min is associated with lower in-hospital mortality compared with non-immediate angiography. MATERIALS AND METHODS: We conducted a retrospective cohort study using a nationwide trauma databank (2019-2020). Adult trauma patients who underwent emergency angiography within 12 h after hospital arrival were included. Patients who underwent surgery before angiography were excluded. Immediate angiography was defined as one performed within 30 min after arrival (door-to-angio time ≤ 30 min). In-hospital mortality and non-operative management (NOM) failure were compared between patients with immediate and non-immediate angiography. Inverse probability weighting with propensity scores was conducted to adjust patient demographics, injury mechanism and severity, vital signs on hospital arrival, and resuscitative procedures. A restricted cubic spline curve was drawn to reveal survival benefits by door-to-angio time. RESULTS: Among 1,455 patients eligible for this study, 92 underwent immediate angiography. Angiography ≤ 30 min was associated with decreased in-hospital mortality (5.0% vs 11.1%; adjusted odds ratio [OR], 0.42 [95% CI, 0.31-0.56]; p < 0.001), as well as lower frequency of NOM failure: thoracotomy and laparotomy after angiography (0.8% vs. 1.8%; OR, 0.44 [0.22-0.89] and 2.6% vs. 6.5%; OR, 0.38 [0.26-0.56], respectively). The spline curve showed a linear association between increasing mortality and prolonged door-to-angio time in the initial 100 min after arrival. CONCLUSION: In trauma patients, immediate angiography ≤ 30 min was associated with lower in-hospital mortality and fewer NOM failures. LEVEL OF EVIDENCE: Level 3b, non randomized controlled cohort/follow up study.


Asunto(s)
Angiografía , Adulto , Humanos , Mortalidad Hospitalaria , Estudios Retrospectivos , Estudios de Seguimiento , Estudios de Cohortes
18.
Brain Tumor Pathol ; 41(2): 50-60, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38332448

RESUMEN

A prompt and reliable molecular diagnosis for brain tumors has become crucial in precision medicine. While Comprehensive Genomic Profiling (CGP) has become feasible, there remains room for enhancement in brain tumor diagnosis due to the partial lack of essential genes and limitations in broad copy number analysis. In addition, the long turnaround time of commercially available CGPs poses an additional obstacle to the timely implementation of results in clinics. To address these challenges, we developed a CGP encompassing 113 genes, genome-wide copy number changes, and MGMT promoter methylation. Our CGP incorporates not only diagnostic genes but also supplementary genes valuable for research. Our CGP enables us to simultaneous identification of mutations, gene fusions, focal and broad copy number alterations, and MGMT promoter methylation status, with results delivered within a minimum of 4 days. Validation of our CGP, through comparisons with whole-genome sequencing, RNA sequencing, and pyrosequencing, has certified its accuracy and reliability. We applied our CGP for 23 consecutive cases of intracranial mass lesions, which demonstrated its efficacy in aiding diagnosis and prognostication. Our CGP offers a comprehensive and rapid molecular profiling for gliomas, which could potentially apply to clinical practices and research primarily in the field of brain tumors.


Asunto(s)
Neoplasias Encefálicas , Variaciones en el Número de Copia de ADN , Metilación de ADN , Glioma , Mutación , Proteínas Supresoras de Tumor , Humanos , Glioma/genética , Glioma/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patología , Metilación de ADN/genética , Proteínas Supresoras de Tumor/genética , Variaciones en el Número de Copia de ADN/genética , Genómica , Metilasas de Modificación del ADN/genética , Regiones Promotoras Genéticas/genética , Enzimas Reparadoras del ADN/genética , Femenino , Masculino , Perfilación de la Expresión Génica , Adulto , Persona de Mediana Edad , Reproducibilidad de los Resultados
20.
Eur J Trauma Emerg Surg ; 50(2): 561-566, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38285212

RESUMEN

PURPOSE: Vital signs are important for predicting clinical outcomes in patients with trauma. However, their accuracy can be affected in older adults because hemodynamic changes are less obvious. This study aimed to examine the usefulness of changes in vital signs during transportation in predicting the need for hemostatic treatments in older patients with trauma. METHODS: This retrospective cohort study was conducted using data from the Japan Trauma Data Bank (2004-2019). Patients aged ≥ 65 years who were hemodynamically stable at the scene were included in this study. The incidence of emergency surgery within 12 h after hospital arrival was compared between patients with delta Shock Index (dSI) > 0.1 and those with dSI ≤ 0.1. Predicting ability was examined after adjusting for patient demographics, comorbidities, vital signs at the scene and on hospital arrival, Injury Severity Score, and abbreviated injury scale in each region. RESULTS: Among the 139,242 patients eligible for the study, 3,701 underwent urgent hemostatic surgery within 12 h. Patients with dSI > 0.1 showed a significantly higher incidence of emergency surgery than those with dSI ≤ 0.1 (871/16,549 [5.3%] vs. 2,830/84,250 [3.4%]; odds ratio (OR), 1.60 [1.48-1.73]; adjusted OR, 1.22 [1.08-1.38]; p = 0.001). The relationship between high dSI and a higher incidence of intervention was observed in patients with hypertension and those with decreased consciousness on arrival. CONCLUSION: High dSI > 0.1 was significantly associated with a higher incidence of urgent hemostatic surgery in older patients.


Asunto(s)
Heridas no Penetrantes , Humanos , Anciano , Femenino , Masculino , Estudios Retrospectivos , Heridas no Penetrantes/cirugía , Heridas no Penetrantes/epidemiología , Japón/epidemiología , Anciano de 80 o más Años , Incidencia , Puntaje de Gravedad del Traumatismo , Signos Vitales , Choque/epidemiología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...