RESUMEN
BACKGROUND: Regularity of menstrual cycles is an important indicator of women's health and fertility, and female workers are exposed to several factors, such as sleep disorders, stress, and shift work, that affect their menstrual regularity. This makes it necessary to comprehensively identify the determinants of menstrual regularity. Therefore, this study identified the factors affecting menstrual regularity among female workers from physiological, psychological, and situational dimensions based on the theory of unpleasant symptoms. METHODS: This was a secondary analysis of the 2010-2012 Korea National Health and Nutrition Examination Survey and utilized the data of 2418 female workers. Based on the theory of unpleasant symptoms, physiological factors included age, age at menarche, childbirth experience, body mass index, and sleep duration. Psychological factors included stress level, depressive mood, and suicidal ideation. Situational factors included education level, household income, consumption of alcohol, engagement in smoking, and work schedule. The χ²-test and hierarchical logistic regression analysis were performed, reflecting the complex sample design. RESULTS: Age at menarche, childbirth experience, and body mass index among physiological factors and education level and work schedule among situational factors were found to be related to menstrual regularity. A higher risk of menstrual irregularities was found among those who had given birth (versus those who had not), had a high age at menarche (versus those with a low age at menarche), were obese (versus those who had a normal body mass index), had elementary school-level or lesser educational achievements (versus those with college graduate-level or higher educational achievements), and who had a shift work schedule (versus those with a fixed schedule). CONCLUSIONS: Intervention is needed for female workers who have these risk factors, and special attention must be paid to female workers who have a shift work schedule. Additionally, since body mass index can be controlled, intervention concerning body mass index is necessary to reduce menstrual irregularity.
Asunto(s)
Índice de Masa Corporal , Menarquia , Trastornos de la Menstruación , Humanos , Femenino , Estudios Transversales , Adulto , República de Corea/epidemiología , Trastornos de la Menstruación/epidemiología , Trastornos de la Menstruación/psicología , Menarquia/psicología , Menstruación/psicología , Menstruación/fisiología , Ciclo Menstrual/psicología , Ciclo Menstrual/fisiología , Adulto Joven , Encuestas Nutricionales , Persona de Mediana Edad , Estrés Psicológico/psicología , Estrés Psicológico/epidemiología , Factores de Edad , Mujeres Trabajadoras/psicología , Mujeres Trabajadoras/estadística & datos numéricosRESUMEN
Background: Oral immunotherapy (OIT) can impose psychological burdens on patients and their parents due to the necessary preparations and repeated adverse reactions. Objective: To investigate changes in quality of life (QoL) and psychological burden in parents of children receiving OIT for food allergy (FA). Methods: Children aged 3-13 years with FA were enrolled. Parents were asked to fill out the Korean versions of the Food Allergy Quality of Life-Parental Burden (FAQL-PB), the Korean versions of the Food Allergy Quality of Life-Parental Form (K-FAQLQ-PF), the Korean versions of the Beck Anxiety Inventory (K-BAI), and the Korean version of the Patient Health Questionnaire-9 (PHQ-9) for depression before OIT (T1), after 2 months of updosing (T2), and after the end of the updosing phase (T3). Results: A total of 111 parents were enrolled. The total FAQL-PB scores were decreased at T2 and T3 compared with those at T1 (all p < 0.001). Greater improvement in the total FAQL-PB score at T2 was noted in parents with a higher parental burden (FAQL-PB score ≥ 74 points) at baseline than in those with a lower parental burden (p = 0.001). Among the K-FAQLQ-PF domains, "food anxiety" scores were decreased at T2 and T3 compared with those at T1 (p = 0.049 and p = 0.030, respectively), whereas there was no change in "social and dietary limitation" and "emotional impact" scores between T1 and T2 and between T1 and T3. However, no differences were observed in K-BAI and PHQ-9 scores between T1 and T2 and between T1 and T3. Conclusion: Our results suggest that OIT improves parental burden and QoL in parents of children with FA.
Asunto(s)
Hipersensibilidad a los Alimentos , Calidad de Vida , Niño , Humanos , Hipersensibilidad a los Alimentos/terapia , Alimentos , Difenhidramina , Inmunoterapia , PadresRESUMEN
There remains continued interest in improving the advanced water oxidation process [e.g., ultraviolet (UV)/hydrogen peroxide (H2O2)] for more efficient and environmentally friendly wastewater treatment. Here, we report the design, fabrication, and performance of graphene oxide (GO, on top)/nickel-doped iron oxyhydroxide (Ni:FeOOH, shell)/silicon nanowires (SiNWs, core) as a new multifunctional photocatalyst for the degradation of common pollutants like polystyrene and methylene blue through enhancing the hydroxyl radical (â¢OH) production rate of the UV/H2O2 system. The photocatalyst combines the advantages of a large surface area and light absorption characteristics of SiNWs with heterogeneous photo-Fenton active Ni:FeOOH and photocatalytically active/charge separator GO. In addition, the built-in electric field of GO/Ni:FeOOH/SiNWs facilitates the charge separation of electrons to GO and holes to Ni:FeOOH, thus boosting the photocatalytic performance. Our photocatalyst increases the â¢OH yield by 5.7 times compared with that of a blank H2O2 solution sample and also extends the light absorption spectrum to include visible light irradiation.
RESUMEN
Magnesium diboride (MgB2) has been explored as an alternative fuel to boron (B) due to its high energy density and the additive effect of magnesium (Mg) to promote B combustion. However, the primary oxidation of MgB2 does not occur unless it decomposes at a high temperature (830 °C), which makes ignition difficult and the reaction slow. Recently, two-dimensional (2D) exfoliated MgB2 nanosheets have attracted increasing attention due to their unique properties and potential applications in various fields. In this study, we investigate the potential of 2D exfoliated MgB2 nanosheets as solid fuels for overcoming the challenges of MgB2 combustion. We analyzed their oxidation behavior and energetic performance through material characterization and combustion tests under slow- and fast-heating conditions and compared their performance with those of bulk MgB2, B nanoparticles, and a B/Mg nanoparticle mixture. This study highlights the potential of MgB2 nanosheets as promising solid fuels with superior energetic properties.
RESUMEN
PURPOSE: This study reviewed existing literature on parental presence in cases of pediatric patients after general anesthesia and explored its effect on emergence delirium (ED) in the postanesthesia care unit (PACU). DESIGN: Systematic review and meta-analysis. METHODS: After protocol registration, we searched the PubMed, EMBASE, CINHAL, Web of Science, SCOPUS, and CENTRAL databases. Two authors independently searched and selected the relevant studies, assessed their risk of bias, and abstracted the data. The primary outcome was ED, and the additional outcome was pain. We provided the narrative synthesis and meta-analysis results. FINDINGS: Of the 296 articles retrieved, 6 were included in the narrative synthesis, and 5 were used for the meta-analysis. Four studies were randomized controlled trials, and two studies were nonrandomized controlled trials. There were 348 pediatric patients in the parental presence group and 314 pediatric patients in the usual care group. Parental presence effectively reduced the ED score (mean difference, -0.58; 95% confidence interval [CI], -0.84 to -0.31; P < .001). The ED incidence rate (log odds ratio, -0.58; 95% CI, -1.24 to 0.09; P = .090) and pain score (standardized mean difference, -0.24; 95% CI, -0.57 to 0.10; P = .163) were lower in the parental presence group than in the usual care group. However, the differences were not statistically significant. CONCLUSIONS: The presence of parents in the PACU can reduce ED in pediatric patients. Therefore, parental presence may be a useful intervention in the PACU.
Asunto(s)
Anestesia General , Delirio del Despertar , Padres , Niño , Preescolar , Humanos , Anestesia General/efectos adversos , Anestesia General/métodos , Anestesia General/estadística & datos numéricos , Delirio del Despertar/epidemiología , Delirio del Despertar/prevención & control , Delirio del Despertar/psicologíaRESUMEN
Focal s egmental glomerulosclerosis (F SGS) can cause protei nuria and loss o f k idney fun ction, leading to e ndstage renal di s ease (ESRD). Podocyte injury is the ce ntral pathophysiologi cal mechanis m of hereditary FSGS. Numerous mutations in genes e ncoding or affe cting the transcriptional regulation of podocyte cell compar tments have been detected in patients with genetic FSGS. Herein, we report a rare case of familial FSGS with an autosomal dominant WT1 mutation. A 63-year- old man developed pro teinuri a; his reading showed over 1g prote in/day. A pa thological diagn osis of FSG S was made after rena l biops y. H is elder brother an d a 36-year- old son also had ESRD. Heterozygous variant of WT1 (NM_024426.4) c.1373G>A (p.Arg458Gln ) mi s sense was dete cted in the patient a nd his son , by whole-exome sequen cing. Although genetic screening is not a par t of routine practice, it s hould be per for med in such cases to a id a ppropriate tre atment options sel ecting, revealing extra ren al symptoms, and family planning.
Asunto(s)
Glomeruloesclerosis Focal y Segmentaria , Fallo Renal Crónico , Masculino , Humanos , Anciano , Persona de Mediana Edad , Adulto , Glomeruloesclerosis Focal y Segmentaria/genética , Mutación Missense , Riñón , Mutación , Fallo Renal Crónico/genética , Proteínas WT1/genéticaRESUMEN
BACKGROUND: Menstrual disturbances harm women's health, and general well-being. As growing evidence highlights the relationship between sleep and menstrual disturbances, it is imperative to comprehensively examine the association between sleep and menstrual disturbance considering the multiple dimensions of sleep. This systematic review aims to identify the association between sleep and menstrual disturbances by evaluating using Buysse's sleep health framework. METHODS: A comprehensive search of the literature was conducted in PubMed, EMBASE, psychINFO, and CINAHL to identify publications describing any types of menstrual disturbances, and their associations with sleep published between January 1, 1988 to June 2, 2022. Quality assessment was conducted using the Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies. The findings were iteratively evaluated menstrual disturbances and their association with sleep using Buysse's sleep health framework. This framework understands sleep as multidimensional concept and provides a holistic framing of sleep including Satisfaction, Alertness during waking hours, Timing of sleep, Efficiency, and Sleep duration. Menstrual disturbances were grouped into three categories: premenstrual syndrome, dysmenorrhea, and abnormal menstrual cycle/heavy bleeding during periods. RESULTS: Thirty-five studies were reviewed to examine the association between sleep and menstrual disturbances. Premenstrual syndrome and dysmenorrhea were associated with sleep disturbances in sleep health domains of Satisfaction (e.g., poor sleep quality), Alertness during waking hours (e.g., daytime sleepiness), Efficiency (e.g., difficulty initiating/maintaining sleep), and Duration (e.g., short sleep duration). Abnormal menstrual cycle and heavy bleeding during the period were related to Satisfaction, Efficiency, and Duration. There were no studies which investigated the timing of sleep. CONCLUSIONS/IMPLICATIONS: Sleep disturbances within most dimensions of the sleep health framework negatively impact on menstrual disturbances. Future research should longitudinally examine the effects of sleep disturbances in all dimensions of sleep health with the additional objective sleep measure on menstrual disturbances. This review gives insight in that it can be recommended to provide interventions for improving sleep disturbances in women with menstrual disturbance.
Asunto(s)
Síndrome Premenstrual , Trastornos del Sueño-Vigilia , Femenino , Humanos , Dismenorrea/complicaciones , Estudios Transversales , Trastornos de la Menstruación/complicaciones , Sueño , Trastornos del Sueño-Vigilia/complicacionesRESUMEN
BACKGROUND: Nurses are particularly at risk of suffering from post-traumatic stress disorder (PTSD) owing to their overwhelming workload, risk of infection, and lack of knowledge about the coronavirus disease 2019 (COVID-19). PTSD negatively affects an individual's health, work performance, and patient safety. This study aims to assess factors related to PTSD among nurses after providing direct care to COVID-19 patients. METHODS: This study is a secondary analysis aimed at identifying factors influencing PTSD among nurses who provided direct care to COVID-19 patients. Data from 168 nurses, collected between October and November 2020, were analyzed. The independent variables were personal, interpersonal, and organizational and COVID-19-related factors (experience of quarantine and direct care of COVID-19 patients), and the dependent variables were PTSD symptoms evaluated based on the PTSD Checklist-5. The nurses' experience of direct care for COVID-19 patients in the designated COVID-19 isolation wards during the first wave of the pandemic (February 2020 to May 2020) was included. RESULTS: Among the nurses, 18.5% exhibited symptoms of PTSD. When providing direct care to a patient in the designated COVID-19 isolation ward, nurses witnessing the death of a patient (p = .001), low level of nurse staffing (p = .008), and inconvenience of electronic health records programs (p = .034) were associated with PTSD symptoms. The experience of quarantine owing to COVID-19 was also associated with PTSD symptoms (p = .034). Additionally, the higher the nurse managers' ability, leadership, and support of nurses in the current ward, the higher the possibility of lowering nurses' PTSD symptoms (p = .006). CONCLUSIONS: Governments and hospitals should prepare and implement organizational intervention programs to improve nurse managers' leadership, nurse staffing levels, and electronic health records programs. Additionally, because nurses who have witnessed the death of a COVID-19 patient or are self-isolating are vulnerable to PTSD, psychological support should be provided.
RESUMEN
Fms-like tyrosine kinase 3 (FLT3) has been verified as a therapeutic target for acute myeloid leukaemia (AML). In this study, we report a series of 2-(1H-indazol-6-yl)-1H-benzo[d]imidazol-5-yl benzamide and phenyl urea derivatives as potent FLT3 inhibitors based on the structural optimisation of previous FLT3 inhibitors. Derivatives were synthesised as benzamide 8a-k, 8n-z, and phenyl urea 8l-m, with various substituents. The most potent inhibitor, 8r, demonstrated strong inhibitory activity against FLT3 and FLT3 mutants with a nanomolar IC50 and high selectivity profiles over 42 protein kinases. In addition, these type II FLT3 inhibitors were more potent against FLT3 mutants correlated with drug resistance. Overall, we provide a theoretical basis for the structural optimisation of novel benzimidazole analogues to develop strong inhibitors against FLT3 mutants for AML therapeutics.
Asunto(s)
Bencimidazoles/farmacología , Diseño de Fármacos , Inhibidores de Proteínas Quinasas/farmacología , Tirosina Quinasa 3 Similar a fms/antagonistas & inhibidores , Bencimidazoles/síntesis química , Bencimidazoles/química , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Humanos , Modelos Moleculares , Estructura Molecular , Mutación , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Relación Estructura-Actividad , Tirosina Quinasa 3 Similar a fms/genética , Tirosina Quinasa 3 Similar a fms/metabolismoRESUMEN
PURPOSE: This study aimed to determine the relationships between occupational stress, sleep disturbance, and presenteeism in shiftwork nurses in South Korea. DESIGN: This cross-sectional study used survey data from 442 shiftwork nurses at two hospitals in South Korea. Data were collected between March 2018 and April 2020. METHODS: A self-reported questionnaire was used to assess shiftwork nurses' demographic and job-related information, presenteeism, occupational stress, and sleep disturbance. Data were analyzed using descriptive statistics, multiple regression, and the PROCESS macro. FINDINGS: The mean presenteeism score was 39.52. Multiple regression analysis revealed that job insecurity, interpersonal conflict, occupational climate, lack of reward, and job demand are significantly associated with presenteeism. Sleep disturbance was related to presenteeism and had a moderating effect on the relationship between occupational stress and presenteeism. CONCLUSIONS: This study indicates that proper occupational climate, positive interpersonal relationships, and adequate sleep can reduce shiftwork presenteeism. Therefore, individual and organizational efforts to alleviate occupational stress and sleep disturbances are essential. CLINICAL RELEVANCE: Organizational support is needed to maintain a positive occupational climate and interpersonal relationships and ameliorate sleep disturbance among shiftwork nurses.
Asunto(s)
Enfermeras y Enfermeros , Estrés Laboral , Trastornos del Sueño-Vigilia , Estudios Transversales , Humanos , Estrés Laboral/epidemiología , Presentismo , Sueño , Trastornos del Sueño-Vigilia/epidemiología , Encuestas y CuestionariosRESUMEN
This paper presents a small-sized, low-power gas sensor system combining a high-electron-mobility transistor (HEMT) device and readout integrated circuit (ROIC). Using a semiconductor-based HEMT as a gas-sensing device, it is possible to secure high sensitivity, reduced complexity, low power, and small size of the ROIC sensor system. Unlike existing gas sensors comprising only HEMT elements, the proposed sensor system has both an ROIC and a digital controller and can control sensor operation through a simple calibration process with digital signal processing while maintaining constant performance despite variations. The ROIC mainly consists of a transimpedance amplifier (TIA), a negative-voltage generator, and an analog-to-digital converter (ADC) and is designed to match a minimum target detection unit of 1 ppm for hydrogen. The prototype ROIC for the HEMT presented herein was implemented in a 0.18 µm complementary metal-oxide-semiconductor (CMOS) process. The total measured power consumption and detection unit of the proposed ROIC for hydrogen gas were 3.1 mW and 2.6 ppm, respectively.
RESUMEN
As members of the MAPK family, c-Jun-N-terminal kinases (JNKs) regulate the biological processes of apoptosis. In particular, the isoform JNK3 is expressed explicitly in the brain at high levels and is involved in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). In this study, we prepared a series of five 6-dihydroxy-1H-benzo[d]imidazoles as JNK3 inhibitors and found them have potential as neuroprotective agents. Following a previous lead scaffold, benzimidazole moiety was modified with various aryl groups and hydroxylation, and the resulting compounds exhibited JNK3 inhibitory activity with improved potency and selectivity. Out of 37 analogues synthesized, (S)-cyclopropyl(3-((4-(2-(2,3-dihydrobenzo[b][1,4]dioxin -6-yl)-5,6-dihydroxy-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino) piperidin-1-yl)methanone (35b) demonstrated the highest JNK3 inhibition (IC50 = 9.7 nM), as well as neuroprotective effects against Aß-induced neuronal cell death. As a protein kinase inhibitor, it also showed excellent selectivity over other protein kinases including isoforms JNK1 (>1000 fold) and JNK2 (-10 fold).
Asunto(s)
Proteína Quinasa 10 Activada por Mitógenos/antagonistas & inhibidores , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacología , Péptidos beta-Amiloides/toxicidad , Animales , Células Cultivadas , Evaluación Preclínica de Medicamentos , Enlace de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Proteína Quinasa 10 Activada por Mitógenos/química , Proteína Quinasa 10 Activada por Mitógenos/metabolismo , Modelos Moleculares , Neuronas/patología , Síndromes de Neurotoxicidad/prevención & control , Fragmentos de Péptidos/toxicidad , RatasRESUMEN
Polo-like kinase 1 (PLK1) plays an important role in cell cycle progression and proliferation in cancer cells. PLK1 also contributes to anticancer drug resistance and is a valuable target in anticancer therapeutics. To identify additional effective PLK1 inhibitors, we performed QSAR studies of two series of known PLK1 inhibitors and proposed a new structure based on a hybridized 3D-QSAR model. Given the hybridized 3D-QSAR models, we designed and synthesized 4-benzyloxy-1-(2-arylaminopyridin-4-yl)-1H-pyrazole-3-carboxamides, and we inspected its inhibitory activities to identify novel PLK1 inhibitors with decent potency and selectivity.
Asunto(s)
Proteínas de Ciclo Celular/química , Técnicas de Química Sintética , Diseño de Fármacos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Inhibidores de Proteínas Quinasas/química , Proteínas Serina-Treonina Quinasas/química , Proteínas Proto-Oncogénicas/química , Relación Estructura-Actividad Cuantitativa , Proteínas de Ciclo Celular/antagonistas & inhibidores , Conformación Molecular , Unión Proteica , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Quinasa Tipo Polo 1RESUMEN
AIM: This study investigated the association between nursing work environment and compassion satisfaction among clinical nurses. BACKGROUND: Nursing work environment and compassion satisfaction are important factors for preventing burnout and decreasing clinical nurse turnover. METHOD: This study used a secondary analysis and obtained data from a previous cross-sectional study. RESULTS: The mean scores (mean ± SD) for the nursing work environment and compassion satisfaction were 2.54 ± 0.34 and 33.40 ± 6.69, respectively. As the results of hierarchical regression, staffing and resources (ß = 0.175, p = .002) and collegial nurse-physician relationships (ß = 0.103, p = .038) were significantly associated with compassion satisfaction. CONCLUSION: Improving the nursing work environment could be an effective way to boost compassion satisfaction among nurses. Therefore, organizational support for adequate human resources and materials and mutual relations among nurses and physicians are needed. IMPLICATIONS FOR NURSING MANAGEMENT: Improvements to the work environment and the management of human resource may increase compassion satisfaction in clinical nurses.
Asunto(s)
Empatía , Enfermeras y Enfermeros/psicología , Lugar de Trabajo/normas , Adulto , Estudios Transversales , Femenino , Humanos , Satisfacción en el Trabajo , Masculino , Enfermeras y Enfermeros/estadística & datos numéricos , Satisfacción Personal , Encuestas y Cuestionarios , Lugar de Trabajo/psicología , Lugar de Trabajo/estadística & datos numéricosRESUMEN
The aim of this study was to examine the association between previous mood episodes and clinical course/functioning in a community sample (National Epidemiological Survey on Alcohol and Related Conditions [NESARC]). Subjects (n = 909) met Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, criteria for bipolar I disorder and provided data on number of previous episode recurrences. Number of previous mood episodes was used to predict outcomes at wave 1 and wave 2 of the NESARC. Previous mood episodes accounted for small but unique variance in outcomes. Recurrence was associated with poorer functioning, psychiatric and medical comorbidity, and increased odds of suicidality, disability, unemployment, and hospitalization at wave 1. Recurrences were associated with greater risk for new onset suicidality, psychiatric comorbidity, disability, unemployment, and poor functioning by wave 2. The course of bipolar disorder does worsen with progressive mood episodes but is attenuated in community, relative to clinical samples. Interventions to prevent future relapse may be particularly important to implement early in the course of illness.
Asunto(s)
Trastorno Bipolar/psicología , Trastornos del Humor/epidemiología , Adulto , Alcoholismo/epidemiología , Alcoholismo/psicología , Trastorno Bipolar/epidemiología , Comorbilidad , Costo de Enfermedad , Personas con Discapacidad/psicología , Personas con Discapacidad/estadística & datos numéricos , Femenino , Encuestas Epidemiológicas , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Trastornos del Humor/psicología , Recurrencia , Suicidio/estadística & datos numéricos , Desempleo/psicología , Desempleo/estadística & datos numéricos , Estados Unidos/epidemiologíaRESUMEN
This study explores the potential of CSF-1R inhibitors as therapeutic agents for neurodegenerative diseases. CSF-1R, a receptor tyrosine kinase primarily expressed in macrophage lineages, plays a pivotal role in regulating various cellular processes. Recent research highlights the significance of CSF-1R inhibition in mitigating neuroinflammation, particularly in Alzheimer's disease, where microglial overactivation contributes to neurodegeneration. The research reveals a series of N-(5-amido-2-methylphenyl)-5-methylisoxazole-3-carboxamide CSF-1R inhibitors, where compounds 7d, 7e, and 9a exhibit outstanding inhibitory activities and selectivity, with IC50 values of 33, 31, and 64 nM, respectively. These most promising compounds in this series were profiled for cellular potency and subjected to in vitro pharmacokinetic profiling. These inhibitors exhibit minimal cytotoxicity, even at higher concentrations, and possess promising blood-brain barrier permeability, making them potential candidates for central nervous system diseases. The investigation into the in vitro ADME properties, including plasma and microsomal stability, reveals that these CSF-1R inhibitors maintain their structural integrity and plasma concentration. This resilience positions them for further development as therapeutic agents for neurodegenerative diseases.
Asunto(s)
Isoxazoles , Enfermedades Neurodegenerativas , Receptor de Factor Estimulante de Colonias de Macrófagos , Humanos , Receptor de Factor Estimulante de Colonias de Macrófagos/química , Receptor de Factor Estimulante de Colonias de Macrófagos/metabolismo , Barrera Hematoencefálica/metabolismo , Proteínas Tirosina Quinasas Receptoras , Inhibidores EnzimáticosRESUMEN
We report herein the potential of colony-stimulating factor-1 receptor (CSF1R) inhibitors as therapeutic agents in neuroinflammatory diseases, with a focus on Alzheimer's disease (AD). Employing a carefully modified scaffold, N-(4-heterocycloalkyl-2-cycloalkylphenyl)-5-methylisoxazole-3-carboxamide, we identify highly selective and potent CSF1R inhibitorsâ7dri and 7dsi. Molecular docking studies shed light on the binding modes of these key compounds within the CSF1R binding site. Remarkably, kinome-wide selectivity assessment underscores the impressive specificity of 7dri for CSF-1R. Notably, 7dri emerges as a potent CSF-1R inhibitor with favorable cellular activity and minimal cytotoxicity among the synthesized compounds. Demonstrating efficacy in inhibiting CSF1R phosphorylation in microglial cells and successfully mitigating neuroinflammation in an in vivo LPS-induced model, 7dri establishes itself as a promising antineuroinflammatory agent.
Asunto(s)
Enfermedades Neurodegenerativas , Humanos , Enfermedades Neurodegenerativas/tratamiento farmacológico , Factor Estimulante de Colonias de Macrófagos , Fosforilación , Simulación del Acoplamiento Molecular , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos , Proteínas Tirosina Quinasas Receptoras/metabolismoRESUMEN
PURPOSE: We aimed to investigate the mediating factors between maternal anxiety and the development of food allergy (FA) in children until 2 years from birth. METHODS: In this longitudinal cohort of 122 mother-child dyads from pregnancy to 24 months of age, we regularly surveyed maternal psychological states, infant feeding data, and allergic symptoms and collected stool samples at 6 months of age for microbiome analysis. Considering the temporal order of data collection, we investigated serial mediating effects and indirect effects among maternal anxiety, dietary diversity (DD), gut microbial diversity, and FA using structural equation modeling. RESULTS: Among the 122 infants, 15 (12.3%) were diagnosed with FA. Increased maternal anxiety between 3 and 6 months after delivery was associated with a lower DD score. Infants with low DD at 4 months showed low gut microbial richness, which was associated with FA development. When the infants were grouped into 4 subtypes, using consensus clustering of 13 gut bacteria significantly associated with maternal anxiety and DD, Prevotella, Eubacterium, Clostridiales and Lachnospiraceae were more abundant in the group with lower FA occurrence. CONCLUSIONS: Postpartum maternal anxiety, mediated by reduced DD and gut microbial diversity, may be a risk factor for the development of FA in infants during the first 2 years of life.
RESUMEN
Hemodialysis patients are susceptible to cardiovascular remodeling, which increases the risk of cardiovascular morbidity and mortality. Circulating extracellular matrix (ECM)-associated molecules increase during cardiovascular remodeling and can be potential biomarkers of adverse cardiovascular outcomes. However, their clinical significance in patients undergoing hemodialysis remain unclear. This study aimed to elucidate the association between circulating ECM-associated molecules and cardiovascular outcomes in patients undergoing hemodialysis. To this end, we measured levels of plasma matrix metalloproteinase (MMP)-2, MMP-9, tenascin-C, and thrombospondin-2 in 372 patients with hemodialysis. Plasma MMP-2 levels were significantly higher in patients with future cardiovascular events than in those without future cardiovascular events (P = 0.004). All measured molecules had significant correlations with amino-terminal pro-brain natriuretic peptide levels, but the correlation coefficient was the strongest for plasma MMP-2 (rho = 0.317, P < 0.001). High plasma MMP-2 levels were predictive of left ventricular (LV) diastolic dysfunction (adjusted odds ratio per a standard deviation increase = 1.48, 95% confidence interval [CI] = 1.05-2.08) and were independently associated with an increased risk of composite cardiovascular events (adjusted hazard ratio per a standard deviation increase = 1.30, 95% CI = 1.04-1.63). In conclusion, high plasma MMP-2 levels are associated with LV diastolic dysfunction and an increased risk of adverse cardiovascular outcomes in hemodialysis patients.